Macrophages: plastic participants in the diagnosis and treatment of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) rank among the most prevalent types of head and neck cancer globally. Unfortunately, a significant number of patients receive their diagnoses at advanced stages, limiting the effectiveness of available treatments. The tumor microenvironment (TME) is a pivotal player in HNSCC development, with macrophages holding a central role. Macrophages demonstrate diverse functions within the TME, both inhibiting and facilitating cancer progression. M1 macrophages are characterized by their phagocytic and immune activities, while M2 macrophages tend to promote inflammation and immunosuppression. Striking a balance between these different polarization states is essential for maintaining overall health, yet in the context of tumors, M2 macrophages typically prevail. Recent efforts have been directed at controlling the polarization states of macrophages, paving the way for novel approaches to cancer treatment. Various drugs and immunotherapies, including innovative treatments based on macrophages like engineering macrophages and CAR-M cell therapy, have been developed. This article provides an overview of the roles played by macrophages in HNSCC, explores potential therapeutic targets and strategies, and presents fresh perspectives on the future of HNSCC treatment.

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.

Insights and implications of sexual dimorphism in osteoporosis.

Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

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.

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.

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.

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.

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system.

BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.

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.

Plasma tRF-16-79MP9PD and tRF-28-OB1690PQR304 as potential biomarkers for 4- to 7-year-old children with obstructive sleep apnea-hypopnea syndrome.

Background: We investigated the expression and the potential value of plasma transfer RNA-derived fragments (tRFs) of children with obstructive sleep apnea-hypopnea syndrome (OSAHS) as screening biomarkers. Methods: At first, we randomly selected five plasma samples from the case group and the control group for high-throughput RNA sequencing. Secondly, we screened two tRFs with different expression between the two groups, amplified it by quantitative reverse transcription-PCR (qRT-PCR) on all samples. Then we analyzed the diagnostic value of the tRFs and their correlation with the clinical data. Results: A total of 50 OSAHS children and 38 healthy controls were included. Our results demonstrated that the plasma levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 were significantly down-regulated in OSAHS children. Receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) of tRF-16-79MP9PD and tRF-28-OB1690PQR304 was 0.7945 and 0.8276. In addition, the AUC of the combination reached 0.8303 with 73.46% and 76.42% sensitivity and specificity. Correlation analysis showed that the degree of tonsil enlargement, hemoglobin (Hb) and triglyceride (TG). were related to the expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304. Multivariable linear regression analysis showed that degree of tonsil enlargement, Hb and TG related to tRF-16-79MP9PD while degree of tonsil enlargement and Hb related to tRF-28-OB1690PQR304. Conclusions: The expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 in the plasma of OSAHS children decreased significantly which were closely related to the degree of tonsil enlargement, Hb and TG, may become novel biomarkers for the diagnosis of pediatric OSAHS.

Carrier-free delivery of thymopentin-regulated injectable nanogels via an enhanced cancer immunity cycle against melanoma metastasis.

Thymopentin (TP5), a clinically used immunomodulatory pentapeptide, can efficiently promote thymocyte differentiation and influence mature T-cell function, thus playing an essential role in the cancer immunotherapy. However, the excellent water solubility and high IC50 of TP5 result in an uncontrolled release behavior, requiring a high loading efficiency to achieve high dosage. Here in, we reported that TP5, combined with specific chemotherapeutic agents, can co-assemble into nanogels due to multiple hydrogen bonding sites. The co-assembly of TP5 with chemotherapeutic agent doxorubicin (DOX) into a carrier-free and injectable chemo-immunotherapy nanogel can enhance the cancer immunity cycle against melanoma metastasis. In this study, the designed nanogel guarantees high drug loading of TP5 and DOX and ensures a site-specific and controlled release of TP5 and DOX with minimal side effects, thus addressing the bottlenecks encountered by current chemo-immunotherapy. Moreover, the released DOX can effectively induce tumor cell apoptosis and immunogenic cell death (ICD) to activate immune initiation. Meanwhile, TP5 can significantly promote the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to amplify the cancer immunity cycle. As a result, this nanogel shows excellent immunotherapeutic efficacy against melanoma metastasis, as well as an effective strategy for TP5 and DOX application.

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.

Protein persulfidation: Rewiring the hydrogen sulfide signaling in cell stress response.

The past few decades have witnessed significant progress in the discovery of hydrogen sulfide (H2S) as a ubiquitous gaseous signaling molecule in mammalian physiology, akin to nitric oxide and carbon monoxide. As the third gasotransmitter, H2S is now known to exert a wide range of physiological and cytoprotective functions in the biological systems. However, endogenous H2S concentrations are usually low, and its potential biologic mechanisms responsible have not yet been fully clarified. Recently, a growing body of evidence has demonstrated that protein persulfidation, a posttranslational modification of cysteine residues (RSH) to persulfides (RSSH) elicited by H2S, is a fundamental mechanism of H2S-mediated signaling pathways. Persulfidation, as a biological switch for protein function, plays an important role in the maintenance of cell homeostasis in response to various internal and external stress stimuli and is also implicated in numerous diseases, such as cardiovascular and neurodegenerative diseases and cancer. In this review, the biological significance of protein persulfidation by H2S in cell stress response is reviewed providing a framework for understanding the multifaceted roles of H2S. A mechanism-guided perspective can help open novel avenues for the exploitation of therapeutics based on H2S-induced persulfidation in the context of diseases.

Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges.

Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

The Promising Hydrogel Candidates for Preclinically Treating Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis.

Significance: Diabetic foot ulcer (DFU) causes high amputation rates owing to its aberrant wound healing. Traditional dressings cannot effectively contribute to DFU healing. Functional hydrogels have been proposed as a promising novel dressing to treat DFU in future, but the evidence for various hydrogels to heal DFU is still ambiguous. Recent Advances: In accordance with PRISMA and CONSORT guidelines, a meta-analysis was performed to evaluate the efficacy of functional hydrogels. Four electronic databases and one website were used for data searching. Twenty-four animal studies and six clinical trials met the inclusion criteria with a total of 399 diabetic murine models and 278 patients with DFU. Critical Issues: Functional hydrogels accelerated the healing progress for DFU and relieved symptoms in patients. According to their characteristics, the functional hydrogels were divided into antioxidant hydrogel (AOH), antibacterial hydrogel (ABH), multifunctional hydrogel (MFH), proangiogenic hydrogel, and hydrogel promoting proliferation (PPH). By network meta-analysis, AOH and MFH were considered the premium options for treating wounds of diabetic patients at whole stage. Future Direction: Functional hydrogels effectively accelerate healing rates in wounds of diabetic animals. Hydrogels of AOH and MFH might become the ideal candidates for clinical trials on DFU treatment, based on the meta-analyses from the reported work. Early treatment with AOH followed a week later with ABH, which might become an advanced strategy for DFU in future. This information is very important for researchers or/and physicians in taking consideration for alternate application of hydrogel dressings. Scope and Significance: The treatment of DFU imposes a huge burden on medical workers. If DFU is not treated properly, patients will have to suffer from amputation and from spiritual agony. Although various topical dressings have been designated for DFU, the healing ability of those dressings is still unknown well. In this review and meta-analysis, we quantitatively evaluated the reported outcomes of functional hydrogels, pure scaffolds, and controls in 2-week interval. Healing ability of various kinds of functional hydrogels was also assessed in different stages of wound, aiming to screen promising candidates for DFU treatment. This information is valuable in designing smart dressings for researchers or/and physicians in future. Translational Relevance: Considering many external factors like formation of bacterial film and internal factors like hyperglycemia, the progress during DFU healing could involve many biochemical aspects. Persistent inflammation, oxidation stress, and impaired angiogenesis lead to prolonged wound healing and even lethal outcomes. Thus, improvement of topical conditions and inhibition of adverse factors will lead to the alleviated morbidity and even mortality. Clinical Relevance: DFU brings about great burden on patients and medical staffs because of high morbidity and poor prognosis. Improper and powerless treatment might induce high rates of amputation and mortality. Functional hydrogels, mimicking extracellular matrices, would provide the tissue with suitable media and functions to promote DFU healing. The application of various types of hydrogels could be a promising solution to heal DFU and reduce adverse events and costs.

Single-cell discovery of the scene and potential immunotherapeutic target in hypopharyngeal tumor environment.

Hypopharyngeal carcinoma is a cancer with the worst prognosis. We constructed the first single-cell transcriptome map for hypopharyngeal carcinoma and explored its underlying mechanisms. We systematically studied single-cell transcriptome data of 17,599 cells from hypopharyngeal carcinoma and paracancerous tissues. We identified categories of cells by dimensionality reduction and performed further subgroup analysis. Focusing on the potential mechanism in the cellular communication of hypopharyngeal carcinoma, we predicted ligand-receptor interactions and verified them via immunohistochemical and cellular experiments. In total, seven cell types were identified, including epithelial and myeloid cells. Subsequently, subgroup analysis showed significant tumor heterogeneity. Based on the pathological type of squamous cell carcinoma, we focused on intercellular communication between epithelial cells and various cells. We predicted the crosstalk and inferred the regulatory effect of cellular active ligands on the surface receptor of epithelial cells. From the top potential pairs, we focused on the BMPR2 receptor for further research, as it showed significantly higher expression in epithelial cancer tissue than in adjacent tissue. Further bioinformatics analysis, immunohistochemical staining, and cell experiments also confirmed its cancer-promoting effects. Overall, the single-cell perspective revealed complex crosstalk in hypopharyngeal cancer, in which BMPR2 promotes its proliferation and migration, providing a rationale for further study and treatment of this carcinoma.