Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma.

BACKGROUND: The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx. RESULTS: Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed. CONCLUSIONS: Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

Analysis of myosin genes in HNSCC and identify MYL1 as a specific poor prognostic biomarker, promotes tumor metastasis and correlates with tumor immune infiltration in HNSCC.

Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

Radiomics analysis of CT imaging improves preoperative prediction of cervical lymph node metastasis in laryngeal squamous cell carcinoma.

OBJECTIVES: To investigate the role of CT radiomics for preoperative prediction of lymph node metastasis (LNM) in laryngeal squamous cell carcinoma (LSCC). METHODS: LSCC patients who received open surgery and lymphadenectomy were enrolled and randomized into primary and validation cohorts at a ratio of 7:3 (325 vs. 139). In the primary cohort, we extracted radiomics features from whole intratumoral regions on venous-phase CT images and constructed a radiomics signature by least absolute shrinkage and selection operator (LASSO) regression. A radiomics model incorporating the radiomic signature and independent clinical factors was established via multivariable logistic regression and presented as a nomogram. Nomogram performance was compared with a clinical model and traditional CT report with respect to its discrimination and clinical usefulness. The radiomics nomogram was internally tested in an independent validation cohort. RESULTS: The radiomics signature, composed of 9 stable features, was associated with LNM in both the primary and validation cohorts (both p < .001). A radiomics model incorporating independent predictors of LNM (the radiomics signature, tumor subsite, and CT report) showed significantly better discrimination of nodal status than either the clinical model or the CT report in the primary cohort (AUC 0.91 vs. 0.84 vs. 0.68) and validation cohort (AUC 0.89 vs. 0.83 vs. 0.70). Decision curve analysis confirmed that the radiomics nomogram was superior to the clinical model and traditional CT report. CONCLUSIONS: The CT-based radiomics nomogram may improve preoperative identification of nodal status and help in clinical decision-making in LSCC. KEY POINTS: • The radiomics model showed favorable performance for predicting LN metastasis in LSCC patients. • The radiomics model may help in clinical decision-making and define patient subsets benefiting most from neck treatment.

Comparison of treatment modalities for selected advanced laryngeal squamous cell carcinoma.

PURPOSE: The authors aimed to clarify the optimal treatment strategy and the indication of different treatments in managing advanced laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 9700 patients with advanced (T3-4aN0-3M0) LSCC who treated with (1) surgery alone, (2) surgery plus adjuvant radiation with or without chemotherapy (aCRT/RT), or (3) definitive CRT/RT was retrieved from the SEER database. The propensity score matching (PSM) was applied to balance confounding factors. Kaplan-Meier method and Cox proportional hazards regression were used to comparing the overall survival (OS) of patients. RESULTS: After optimal matching, 907 patients were screened from each treatment cohort. Kaplan-Meier and multivariate analyses presented that patients treated with surgery plus aCRT/CT had significantly longer OS than those treated with either surgery alone or CRT/RT, even after PSM. However, significant interactions were tested in treatment effects in stratified analyses of the primary subsite, T stage, N stage, and insurance status (PInteraction < 0.05 for all). Specifically, surgery plus aCRT/CT significantly improved the OS of patients with supraglottic, T4a, and N + tumors (P < 0.001 for all), while three treatment modalities achieved equal OS rates for patients with glottic, T3, and N0 tumors (P > 0.05 for all). Besides, supraglottic tumors presented a poorer prognosis than glottic subsite. CONCLUSION: Current study suggests that surgery with aCRT/RT is the preferred initial therapy for patients with T4a tumors, whereas patients with T3 tumors could be treated with either surgery (followed by aCRT/RT if it presents N +) or definitive CRT/RT for achieving laryngeal preservation. More-intense treatment should be emphasized for advanced supraglottic cancer.

A novel surgical approach for hypopharyngeal carcinoma resection via the paraglottic space.

BACKGROUND: Conservative surgery has proven advantageous in controlling hypopharyngeal squamous cell carcinoma (HSCC) and preserving speech and swallowing function in carefully selected patients, typically with early T-stages diseases. A variety of modified surgical procedures or techniques have been proposed. METHODS: In this study, we present a novel surgical approach for hypopharyngeal carcinoma resection utilizing the paraglottic space. RESULTS: The paraglottic space approach can help expose neoplasms under direct vision and save mucosa during surgery while sufficiently preserving laryngeal function, thus benefiting postoperative swallowing and reducing complications. A large cohort of 426 patients with HSCC underwent surgical treatment at our institution using this approach, demonstrating an overall survival (OS) rate of 52.3% and low incidences of postoperative complications. CONCLUSIONS: This surgical approach can be applied in patients with the lesions that do not involve the paraglottic space.

Effect of up-regulation of circMATR3 on the proliferation, metastasis, progression and survival of hypopharyngeal carcinoma.

Increasing number of circular RNAs (circRNAs) have been reported to play important role in gene regulation, carcinogenesis and pathogenesis in various cancers. However, the biological functions and underlying molecular mechanisms of circRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain elusive. Thus, secondary circRNA-seq profiling was performed to identify the differentially expressed circRNAs between HSCC tissues and adjacent normal tissues, and the expression level of circMATR3 (derived from human gene matrin3 (MATR3), has_circRNA_0008922) was confirmed by qRT-PCR. Proliferation of HSCC cells was detected by cell counting kit-8 (CCK8) assay, apoptosis and the cell cycle were analysed by flow cytometry, and the migration and invasion of HSCC cells was determined by transwell assay. Bioinformatics analysis was conducted to predict possible pathways and potential miRNA targets of circMATR3. We found that circMATR3 was up-regulated in HSCC tissues, and abundant circMATR3 expression was markedly correlated with late T classification, advanced clinical stage, greater lymph node metastasis, and poor prognosis. Furthermore, knock-down of circMATR3 significantly inhibited proliferation, migration and invasion of HSCC cells, whereas silencing of circMATR3 induced cell apoptosis. Our analysis predicted that circMATR3 may participate in cancer-related pathways by serving as miRNA sponges. In conclusion, our findings first identified the oncogenic roles of circMATR3 in promoting the progression of HSCC and demonstrated that circMATR3 may be a novel prognostic marker and therapeutic target for HSCC.

A 3-miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post-operative radiotherapy.

Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post-operative radiotherapy, we used miRNA microarray and qRT-PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan-Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR-200a-3p, miR-30b-5p, miR-3161, miR-3605-5p, miR-378b and miR-4451 were up-regulated, while miR-200c-3p, miR-429 and miR-4701 were down-regulated after validation. Moreover, the patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly worse overall survival (OS) and disease-specific survival (DSS) than did those with low expression (log-rank P < .05). Patients with a high-risk score had significant worse OS and DSS than those with low-risk score. Finally, after adjusting for other important prognostic confounders, patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly high risk of overall death and death owing to HSCC and patients with a high-risk score has approximately 2-fold increased risk in overall death and death owing to HSCC compared with those with a low-risk score. These findings indicated that the 3-miRNA-based signature may be a novel independent prognostic biomarker for patients given surgery and post-operative radiotherapy, supporting that these miRNAs may jointly predict survival of HSCC.

The Long Noncoding RNA TUG1 Promotes Laryngeal Cancer Proliferation and Migration.

BACKGROUND/AIMS: Researchers have shown that long noncoding RNAs are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). However, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in the pathogenesis of LSCC remains unclear, although it is recognized as an oncogenic regulator for several types of squamous cell carcinoma. METHODS: qRT-PCR was performed to measure the expression of TUG1 in LSCC tissues and cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to measure the effect of TUG1 on cell proliferation. Transwell assay and flow cytometry were employed to determine the effect of TUG1 on cell migration and invasion. Western-blot were performed to explore the relation of TUG1 and p53 mRNA. RESULTS: Higher TUG1 expression in LSCC than in paired normal tumor-adjacent tissue specimens (N = 64) was observed using quantitative real-time polymerase chain reaction. Also, high TUG1 expression was positively associated with advanced T category, worse lymph node metastasis and late clinical stage. Furthermore, in vitro experiments demonstrated that silencing of TUG1 markedly inhibited proliferation, cell-cycle progression, migration, and invasion of LSCC cells, whereas depletion of TUG1 led to increased apoptosis. CONCLUSION: These findings demonstrated that upregulated TUG1 expression exerted oncogenic effects by promoting proliferation, migration, and invasion, and inhibiting apoptosis in LSCC cells.

Upregulation of the long noncoding RNA UCA1 affects the proliferation, invasion, and survival of hypopharyngeal carcinoma.

BACKGROUND: Several long noncoding RNAs (lncRNAs) are involved in oncogenesis. METHODS AND RESULTS: Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells. CONCLUSIONS: Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.

Inhibition of CDK9 induces apoptosis and potentiates the effect of cisplatin in hypopharyngeal carcinoma cells.

Myeloid cell leukemia-1 (Mcl-1) plays an important role in survival, chemo- and radioresistance of head and neck squamous cell carcinoma (HNSCC). Cyclin-dependent kinase 9/cyclin T (CDK9) promotes excessive production of multiple pro-survival proteins including Mcl-1, leading to impaired apoptosis of cancer cells. As such, CDK9 is an emerging therapeutic target in cancer therapy. We herein report the first study of targeting CDK9 as a treatment strategy for hypopharyngeal squamous cell carcinoma (HSCC), an aggressive malignancy associated with one of the worst prognoses within HNSCC. We showed that mRNA levels of Mcl-1 were significantly higher in HSCC tumor tissues than in the adjacent non-tumor mucosae. In addition, the levels of Mcl-1 mRNA correlated with the tumor size and clinical stage of HSCC patients. CDKI-73, a potent CDK9 inhibitor, was capable of downregulating the expression of Mcl-1 in the HSCC cells by suppression of the CDK9 mediated phosphorylation of RNA polymerase II. CDKI-73 effectively induced apoptosis as a single agent and synergized anti-tumor activity of cisplatin in HSCC cells. Taken together, our study presents compelling evidence for developing CDK9 inhibitors, such as CDKI-73, as new therapeutic strategy for HSCC.

Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM). METHOD: In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations. RESULTS: The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients. CONCLUSION: These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

Preservation of laryngeal function improves outcomes of patients with hypopharyngeal carcinoma.

This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had significantly better overall survival (log-rank, P = 0.005) and a lower risk of death than those without LF preservation (HR 0.62, 95% CI 0.43-0.97), after multivariable adjustment. Treatment with surgery in combination with radiotherapy is still the favorable choice for patients with hypopharyngeal carcinoma. The maximal restoration of pharyngoesophageal continuity and function improves survival for patients whose tumors are excised completely for the preservation of LF and laryngeal and pharyngeal reconstruction.

Automated Monitoring System for Suspended Photocatalytic Batch Reactions Based on Online Circulatory Spectrophotometry.

Employing an automated monitoring system (AMS) for data acquisition offers benefits, such as reducing the workload, in the kinetic study of suspended photocatalytic batch reactions. However, the current methods in this field tend to narrowly focus on the substrate and often overlook the optical characteristics of both the mixture and solid particles. To address this limitation, in this study, we propose a novel AMS based on online circulatory spectrophotometry (OCS) and incorporate debubbling, aeration, and segmented flow (DAS), named DAS-OCS-AMS. Initially, a debubbler is introduced to mitigate the issue of signal noise caused by bubbles (SNB). Subsequently, an aerated and segmented device is developed to address the issue of particle deposition on the inner wall of the pipeline (PDP) and on the windows of the flow cell (PDW). The proposed DAS-OCS-AMS is applied to monitor the kinetics of the photocatalytic degradation of Acid Orange Ⅱ by TiO2 (P25), and its results are compared with those obtained using the traditional OCS-AMS. The comparative analysis indicates that the proposed DAS-OCS-AMS effectively mitigates the influence of SNB, PDP, and PDW, yielding precise results both for the mixture and solid particles. The DAS-OCS-AMS provides a highly flexible universal framework for online circulatory automated monitoring and a robust hardware foundation for subsequent data processing research.

Comparing three-dimensional and two-dimensional deep-learning, radiomics, and fusion models for predicting occult lymph node metastasis in laryngeal squamous cell carcinoma based on CT imaging: a multicentre, retrospective, diagnostic study.

Background: The occult lymph node metastasis (LNM) of laryngeal squamous cell carcinoma (LSCC) affects the treatment and prognosis of patients. This study aimed to comprehensively compare the performance of the three-dimensional and two-dimensional deep learning models, radiomics model, and the fusion models for predicting occult LNM in LSCC. Methods: In this retrospective diagnostic study, a total of 553 patients with clinical N0 stage LSCC, who underwent surgical treatment without distant metastasis and multiple primary cancers, were consecutively enrolled from four Chinese medical centres between January 01, 2016 and December 30, 2020. The participant data were manually retrieved from medical records, imaging databases, and pathology reports. The study cohort was divided into a training set (n = 300), an internal test set (n = 89), and two external test sets (n = 120 and 44, respectively). The three-dimensional deep learning (3D DL), two-dimensional deep learning (2D DL), and radiomics model were developed using CT images of the primary tumor. The clinical model was constructed based on clinical and radiological features. Two fusion strategies were utilized to develop the fusion model: the feature-based DLRad_FB model and the decision-based DLRad_DB model. The discriminative ability and correlation of 3D DL, 2D DL and radiomics features were analysed comprehensively. The performances of the predictive models were evaluated based on the pathological diagnosis. Findings: The 3D DL features had superior discriminative ability and lower internal redundancy compared to 2D DL and radiomics features. The DLRad_DB model achieved the highest AUC (0.89-0.90) among all the study sets, significantly outperforming the clinical model (AUC = 0.73-0.78, P = 0.0001-0.042, Delong test). Compared to the DLRad_DB model, the AUC values for the DLRad_FB, 3D DL, 2D DL, and radiomics models were 0.82-0.84 (P = 0.025-0.46), 0.86-0.89 (P = 0.75-0.97), 0.83-0.86 (P = 0.029-0.66), and 0.79-0.82 (P = 0.0072-0.10), respectively in the study sets. Additionally, the DLRad_DB model exhibited the best sensitivity (82-88%) and specificity (79-85%) in the test sets. Interpretation: The decision-based fusion model DLRad_DB, which combines 3D DL, 2D DL, radiomics, and clinical data, can be utilized to predict occult LNM in LSCC. This has the potential to minimize unnecessary lymph node dissection and prophylactic radiotherapy in patients with cN0 disease. Funding: National Natural Science Foundation of China, Natural Science Foundation of Shandong Province.

Arbitrary Construction of Versatile NIR-Driven Microrobots.

Emerging light-driven micro/nanorobots (LMNRs) showcase profound potential for sophisticated manipulation and various applications. However, the realization of a versatile and straightforward fabrication technique remains a challenging pursuit. This study introduces an innovative bulk heterojunction organic semiconductor solar cell (OSC)-based spin-coating approach, aiming to facilitate the arbitrary construction of LMNRs. Leveraging the distinctive properties of a near-infrared (NIR)-responsive organic semiconductor heterojunction solution, this technique enables uniform coating across various dimensional structures (0D, 1D, 2D, 3D) to be LMNRs, denoted as "motorization." The film, with a slender profile measuring ≈140 nm in thickness, effectively preserves the original morphology of objects while imparting actuation capabilities exceeding hundreds of times their own weight. The propelled motion of these microrobots is realized through NIR-driven photoelectrochemical reaction-induced self-diffusiophoresis, showcasing a versatile array of controllable motion profiles. The strategic customization of arbitrary microrobot construction addresses specific applications, ranging from 0D microrobots inducing living crystal formation to intricate, multidimensional structures designed for tasks such as microplastic extraction, cargo delivery, and phototactic precise maneuvers. This study advances user-friendly and versatile LMNR technologies, unlocking new possibilities for various applications, signaling a transformative era in multifunctional micro/nanorobot technologies.

[A case of pediatric tracheal inflammatory myofibroblastic tumor].

Inflammatory myofibroblastic tumor is a rare tumor of mesenchymal origin. A case of intratracheal inflammatory myofibroblastic tumor in a male child was reported. The clinical characteristics, diagnosis, treatment and prognosis of the disease were reviewed based on the literature, and a differential diagnosis between inflammatory myofibroblastic tumor and hamartoma was performed to ultimately confirm the nature of the tumor in the child.

CYP4F12 is a potential biomarker and inhibits cell migration of head and neck squamous cell carcinoma via EMT pathway.

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor of head and neck. Due to the insidious nature of HNSC and the lack of effective early diagnostic indicators, the development of novel biomarkers to improve patient prognosis is particularly urgent. In this study, we explored and validated the correlation between cytochrome P450 family 4 subfamily F member 12 (CYP4F12) expression levels and HNSC progression using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and collected patient samples. We analyzed the association of CYP4F12 expression with clinicopathological features, immune correlation and prognosis. Finally, we analyzed the correlation between CYP4F12 and pathways, and verified by experiments. The results showed that CYP4F12 was low expressed in tumor tissues, participated in a variety of phenotypic changes of HNSC and affected immune cell infiltration. Pathway analysis indicated that CYP4F12 may play a key role in tumor cell migration and apoptosis. Experimental results showed that over-expression of CYP4F12 inhibited cell migration and enhanced the adhesion between cells and matrix by inhibiting epithelial-mesenchymal transition (EMT) pathway in HNSC cells. In conclusion, our study provided insights into the role of CYP4F12 in HNSC and revealed that CYP4F12 may be a potential therapeutic target for HNSC.

Preliminary study based on methylation and transcriptome gene sequencing of lncRNAs and immune infiltration in hypopharyngeal carcinoma.

Background: Hypopharyngeal squamous cell cancer (HSCC) is one of the most malignant tumors of the head and neck. It is not easy to detect in the early stage due to its hidden location; thus, lymph node metastasis is highly likely at diagnosis, leading to a poor prognosis. It is believed that epigenetic modification is related to cancer invasion and metastasis. However, the role of m6A-related lncRNA in the tumor microenvironment (TME) of HSCC remains unclear. Methods: The whole transcriptome and methylation sequencing of 5 pairs of HSCC tissues and adjacent tissues were performed to identify the methylation and transcriptome profiles of lncRNAs. The biological significance of lncRNAs differentially expressing the m6A peak was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. By constructing an m6A lncRNA-microRNA network, the mechanism of m6A lncRNAs in HSCC was analyzed. The relative expression levels of selected lncRNAs were examined by quantitative polymerase chain reaction. The CIBERSORT algorithm was used to evaluate the relative proportion of immune cell infiltration in HSCC and paracancerous tissues. Results: Based on an in-depth analysis of the sequencing results, 14413 differentially expressed lncRNAs were revealed, including 7329 up-regulated and 7084 down-regulated lncRNAs. Additionally, 4542 up-methylated and 2253 down-methylated lncRNAs were detected. We demonstrated methylation patterns and gene expression profiles of lncRNAs of HSCC transcriptome. In the intersection analysis of lncRNAs and methylated lncRNAs, 51 lncRNAs with up-regulated transcriptome and methylation and 40 lncRNAs with down-regulated transcriptome and methylation were screened, and significantly differentiated lncRNAs were further studied. In the immune cell infiltration analysis, B cell memory was significantly elevated in cancer tissue, while γδT cell amount was significantly decreased. Conclusion: m6A modification of lncRNAs might be involved in HSCC pathogenesis. Infiltration of immune cells in HSCC might provide a new direction for its treatment. This study provides new insights for exploring the possible HSCC pathogenesis and searching for new potential therapeutic targets.