Group-III nitride heteroepitaxial films approaching bulk-class quality.

III-nitride wide bandgap semiconductors are promising materials for modern optoelectronics and electronics. Their application has progressed greatly thanks to the continuous quality improvements of heteroepitaxial films grown on large-lattice-mismatched foreign substrates. But compared with bulk single crystals, there is still tremendous room for the further improvement of the material quality. Here we show a paradigm to achieve high-quality III-nitride heteroepitaxial films by the controllable discretization and coalescence of columns. By adopting nano-patterned AlN/sapphire templates with regular hexagonal holes, discrete AlN columns coalesce with uniform out-of-plane and in-plane orientations guaranteed by sapphire nitridation pretreatment and the ordered lateral growth of cleavage facets, which efficiently suppresses the regeneration of threading dislocations during coalescence. The density of dislocation etch pits in the AlN heteroepitaxial film reaches 3.3 × 104 cm-2, close to the present available AlN bulk single crystals. This study facilitates the growth of bulk-class quality III-nitride films featuring low cost and scalability.

Chiral whispering gallery modes and chirality-dependent symmetric optical force induced by a spin-polarized surface wave of photonic Dirac semimetal.

Dirac degeneracy is a fourfold band crossing point in a three-dimensional momentum space, which possesses Fermi-arc-like surface states, and has extensive application prospects. In this work, we systematically study the exceptional effects of the robust chiral surface wave supported by photonic Dirac semimetal acts on the dielectric particles. Theoretical results show that orthogonal electromagnetic modes and helical or chiral whispering gallery modes (WGMs) of dielectric particles can be efficiently excited by the unidirectional spin-polarized surface wave. More importantly, optical forces exerted by the spin-polarized surface wave exhibit chirality-dependent symmetric behavior and high chiral Q factor with precise size selectivity. Our findings may provide potential applications in the area of chiral microcavity, spin optical devices, and optical manipulations.

Unspliced XBP1 Counteracts ß-Catenin to Inhibit Vascular Calcification.

BACKGROUND: Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the XBP1u (unspliced XBP1) and XBP1s (spliced XBP1) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear. METHODS: We aim to investigate the role of XBP1u in vascular calcification. XBP1u protein levels were reduced in high phosphate-induced calcified vascular smooth muscle cells, calcified aortas from mice with adenine diet-induced chronic renal failure, and calcified radial arteries from patients with chronic renal failure. RESULTS: Inhibition of XBP1u rather than XBP1s upregulated in the expression of the osteogenic markers Runx2 (runt-related transcription factor 2) and Msx2 (msh homeobox 2), and exacerbated high phosphate-induced vascular smooth muscle cell calcification, as verified by calcium deposition and Alizarin red S staining. In contrast, XBP1u overexpression in high phosphate-induced vascular smooth muscle cells significantly inhibited osteogenic differentiation and calcification. Consistently, smooth muscle cell-specific XBP1 deficiency in mice markedly aggravated the adenine diet- and 5/6 nephrectomy-induced vascular calcification compared with that in the control littermates. Further interactome analysis revealed that XBP1u is bound directly to ß-catenin, a key regulator of vascular calcification, via amino acid (aa) 205-230 in its C-terminal degradation domain. XBP1u interacted with ß-catenin to promote its ubiquitin-proteasomal degradation and thus inhibited ß-catenin/TCF (T-cell factor)-mediated Runx2 and Msx2 transcription. Knockdown of ß-catenin abolished the effect of XBP1u deficiency on vascular smooth muscle cell calcification, suggesting a ß-catenin-mediated mechanism. Moreover, the degradation of ß-catenin promoted by XBP1u was independent of GSK-3ß (glycogen synthase kinase 3ß)-involved destruction complex. CONCLUSIONS: Our study identified XBP1u as a novel endogenous inhibitor of vascular calcification by counteracting ß-catenin and promoting its ubiquitin-proteasomal degradation, which represents a new regulatory pathway of ß-catenin and a promising target for vascular calcification treatment.

In Situ Ligand-Transformation-Assisted Assembly of a Polyoxometalate and Silver-Phosphine Oxide Cluster for Colorimetric Detection of Phenol Contaminants.

In situ ligand transformation strategies represent an efficient pathway for constructing function-oriented polyoxometalate (POM)-based crystalline materials. Herein, three POM-based hybrid networks were synthesized through in situ transformation of the phosphine ligand, formulated as [Ag(dppeo)6][H2PMo12O40]·5H2O (1), [Ag(dedpo)]4[SiW12O40]·6H2O (2), and [Ag(dppeo)]3[PW12O40]·3H2O (3) (dedpo = (2-(diphenylphosphaneyl)ethyl)diphenylphosphine oxide; dppeo = ethane-1,2-diylbis(diphenylphosphine oxide)). During the synthesis of these compounds, the 1,2-diphenylphosphine ethane molecule underwent in situ oxidation, transforming into dppeo and dedpo ligands, respectively. Compound 1 features a supramolecular architecture assembled from [Ag(dppeo)3]+/[Ag2(dppeo)6]2+ cationic clusters with disordered Ag centers and protonated [H2PMo12O40]- anions. Compound 2 presents a 3-D POM-supported metal-organic framework consisting of binuclear [Ag(dedpo)]22+ units, {-dedpo-Ag-dedpo-} chains, and [SiW12O40]4- polyoxoanions. Compound 3 displays a 2-D layered structure formed by {-dppeo-Ag3-dppeo-} chains and [PW12O40]3- clusters. Pronounced argentophilic interactions are observed in compounds 1 and 3. The three compounds demonstrate satisfactory heterogeneous catalytic activity in the colorimetric detection reactions toward phenol pollutants with detection limits of 1.73, 1.92, and 4.6 µM, respectively. Additionally, compounds 1-3 show high anti-interference capabilities and high sensitivity in differentiating phenol from its halogenated derivatives. This work presents some guidance for designing specific function-oriented POM-based materials via an in situ ligand transformation strategy.

Full-length transcriptome assembly of black amur bream (Megalobrama terminalis) as a reference resource.

BACKGROUND: The genus Megalobrama holds significant economic value in China, with M. terminalis (Black Amur bream) ranking second in production within this group. However, lacking comprehensive genomic and transcriptomic data has impeded research progress. This study aims to fill this gap through an extensive transcriptomic analysis of M. terminalis. METHODS AND RESULTS: We utilized PacBio Isoform Sequencing to generate 558,998 subreads, totaling 45.52 Gb, which yielded 22,141 transcripts after rigorous filtering and clustering. Complementary Illumina short-read sequencing corrected 967,114 errors across these transcripts. Our analysis identified 12,426 non-redundant isoforms, with 11,872 annotated in various databases. Functional annotation indicated 11,841 isoforms matched entries in the NCBI non-redundant protein sequences database. Gene Ontology analysis categorized 10,593 isoforms, revealing strong associations with cellular processes and binding functions. Additionally, 8203 isoforms were mapped to pathways in the Kyoto Encyclopedia of Genes and Genomes, highlighting significant involvement in immune system processes and complement cascades. We notably identified key immune molecules such as alpha-2-macroglobulin and complement component 3, each with multiple isoforms, underscoring their potential roles in the immune response. Our analysis also uncovered 853 alternative splicing events, predominantly involving retained introns, along with 672 transcription factors and 426 long non-coding RNAs. CONCLUSIONS: The high-quality reference transcriptome generated in this study provides a valuable resource for comparative genomic studies within the Megalobrama genus, supporting future research to enhance aquaculture stocks.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the Field Setting: A Case Report From China.

BACKGROUND: The widespread use of agricultural machinery in China has increased the incidence of agricultural machinery-related injuries, posing challenges to on-site medical rescue. This study explores resuscitative endovascular balloon occlusion of the aorta (REBOA) as a life-saving intervention for a patient with severe trauma from agricultural machinery. CASEPRESENTATION: This study reviews the emergency medical response for a 70-year-old male who suffered machinery entanglement injuries in an agricultural field in western China. The intervention involved a tiered multidisciplinary medical response, including the implementation of REBOA. CONCLUSION: This case demonstrates the successful use of REBOA in the prehospital setting in China. While prehospital REBOA use is rare, it is increasingly reported in both military and civilian contexts in austere environments in different countries. Further research is required to validate the feasibility and efficacy of REBOA as a prehospital resuscitation strategy.

The suppression of hyperlipid diet-induced ferroptosis of vascular smooth muscle cells protests against atherosclerosis independent of p53/SCL7A11/GPX4 axis.

Ferroptosis as a novel programmed cell death that involves metabolic dysfunction due to iron-dependent excessive lipid peroxidation has been implicated in atherosclerosis (AS) development characterized by disrupted lipid metabolism, but the atherogenic role of ferroptosis in vascular smooth muscle cells (VSMCs), which are principal components of atherosclerotic plaque fibrous cap, remains unclear. The aim of this study was to determine the effects of ferroptosis on AS induced by lipid overload, and the effects of that on VSMCs ferroptosis. We found intraperitoneal injection of Fer-1, a ferroptosis inhibitor, ameliorated obviously high-fat diet-induced high plasma levels of triglycerides, total cholesterol, low-density lipoprotein, glucose and atherosclerotic lesions in ApoE-/- mice. Moreover, in vivo and in vitro, Fer-1 reduced the iron accumulation of atherosclerotic lesions through affecting the expression of TFR1, FTH, and FTL in VSMCs. Interestingly, Fer-1 did augment nuclear factor E2-related factor 2/ferroptosis suppressor protein 1 to enhance endogenous resistance to lipid peroxidation, but not classic p53/SCL7A11/GPX4. Those observations indicated inhibition of VSMCs ferroptosis can improve AS lesions independent of p53/SLC7A11/GPX4, which preliminarily revealed the potential mechanism of ferroptosis in aortic VSMCs on AS and provided new therapeutic strategies and targets for AS.

Combined transcriptome and metabolome analysis reveal key regulatory genes and pathways of feed conversion efficiency of oriental river prawn Macrobrachium nipponense.

BACKGROUND: Oriental river prawn Macrobrachium nipponense is an economically important aquaculture species in China, Japan, and Vietnam. In commercial prawn farming, feed cost constitutes about 50 to 65% of the actual variable cost. Improving feed conversion efficiency in prawn culture will not only increase economic benefit, but also save food and protect the environment. The common indicators used for feed conversion efficiency include feed conversion ratio (FCR), feed efficiency ratio (FER), and residual feed intake (RFI). Among these, RFI is much more suitable than FCR and FER during the genetic improvement of feed conversion efficiency for aquaculture species. RESULTS: In this study, the transcriptome and metabolome of hepatopancreas and muscle of M. nipponense from high RFI low RFI groups, which identified after culture for 75 days, were characterized using combined transcriptomic and metabolomic analysis. A total of 4540 differentially expressed genes (DEGs) in hepatopancreas, and 3894 DEGs in muscle were identified, respectively. The DEGs in hepatopancreas were mainly enriched in KEGG pathways including the metabolism of xenobiotics by cytochrome P450 (down-regulated), fat digestion and absorption (down-regulated) and aminoacyl-tRNA biosynthesis (up-regulated), etc. The DEGs in muscle were mainly enriched in KEGG pathways including the protein digestion and absorption (down-regulated), glycolysis/gluconeogenesis (down-regulated), and glutathione metabolism (up-regulated), etc. At the transcriptome level, the RFI of M. nipponense was mainly controlled in biological pathways such as the high immune expression and the reduction of nutrients absorption capacity. A total of 445 and 247 differently expressed metabolites (DEMs) were identified in the hepatopancreas and muscle, respectively. At the metabolome level, the RFI of M. nipponense was affected considerably by amino acid and lipid metabolism. CONCLUSIONS: M. nipponense from higher and lower RFI groups have various physiological and metabolic capability processes. The down-regulated genes, such as carboxypeptidase A1, 6-phosphofructokinase, long-chain-acyl-CoA dehydrogenase, et. al., in digestion and absorption of nutrients, and the up-regulated metabolites, such as aspirin, lysine, et. al., in response to immunity could be potential candidate factors contributed to RFI variation for M. nipponense. Overall, these results would provide new insights into the molecular mechanism of feed conversion efficiency and assist in selective breeding to improve feed conversion efficiency in M. nipponense.

Green Approach for Rare Earth Element (REE) Recovery from Coal Fly Ash.

Due to the growing demands of rare earth elements (REEs) and the vulnerability of REEs to potential supply disruption, there have been increasing interests in recovering REEs from waste streams such as coal fly ash (CFA). Meanwhile, CFA as a large industrial waste stream in the United States (U.S.) poses significant environmental and economic burdens. Recovery of REEs from CFA is a promising solution to the REE scarcity issue and also brings opportunities for CFA management. This study demonstrates a green system for REE recovery from Class F and C CFA that consists of three modules: REE leaching using citrate, REE separation and concentration using oxalate, and zeolite synthesis using secondary wastes from Modules I and II. In Module I, ∼10 and 60% REEs were leached from the Class F and C CFA samples, respectively, using citrate at pH 4. In Module II, the addition of oxalate selectively precipitated and concentrated REEs from the leachate via the formation of weddellite (CaC2O4·2H2O), while other trace metals remained in solution. In Module III, zeolite was synthesized using wastes from Modules I and II. This study is characterized by the successful recovery of REEs and upcycling of secondary wastes, which addresses both REE recovery and CFA management challenges.

Prognostic value of tumor-infiltrating immune cells in clinical early-stage oral squamous cell carcinoma.

BACKGROUND: Tumor-infiltrating immune cells (TIICs) are critical components of tumor immune microenvironment (TIME), which play crucial roles during tumor initiation, development, and progression. However, the prognostic value of TIICs is still not well documented in clinical early-stage oral squamous cell carcinoma (OSCC). In this study, we aimed to assess the prognostic value of TIICs in clinical early-stage OSCC and develop a nomogram based on TIICs to predict the prognosis. METHODS: Eighty patients with clinical early-stage (cT1,2N0M0) OSCC were enrolled in this study. Immunohistochemical staining was performed to evaluate the infiltration of TIICs, including CD8+ T cells, CD57+ NK cells, CD163+ macrophage, and CD20+ B cells. Overall survival (OS) and disease-free survival (DFS) curves were plotted by the Kaplan-Meier method. Cox's proportional hazards regression models were performed to assess the prognostic value of TIICs. Finally, a nomogram was established to predict the OS based on TIICs infiltration and assessed by concordance index (C-index) and calibration curve. RESULTS: High infiltrations of CD57+ NK cells and CD20+ B cells indicated a better OS in clinical early-stage OSCC. Moreover, high infiltration of CD20+ B cells favored a longer DFS. Of note, low infiltrations of CD57+ NK cells and CD20+ B cells were independent prognostic factors for poor OS in clinical early-stage OSCC. The nomogram that combined CD57+ NK cells with CD20+ B cells could predict the OS in clinical early-stage OSCC, and the C-index was 0.801 (95% CI: 0.679-0.924). The calibration plot showed that prediction and observation are well matched. CONCLUSIONS: High infiltration of CD57+ NK cells and CD20+ B cells indicate a favorable OS in clinical early-stage OSCC. The nomogram constructed based on TIICs might be used for predicting the prognosis in clinical early-stage OSCC.

Synergistic between autotrophic and heterotrophic microorganisms for denitrification using bio-S as electron donor.

In recent years, biological sulfur (bio-S) was employed in sulfur autotrophic denitrification (SAD) in which autotrophic Thiobacillus denitrificans and heterotrophic Stenotrophomonas maltophilia played a key role. The growth pattern of T.denitrificans and S.maltophilia exhibited a linear relationship between OD600 and CFU when OD600 < 0.06 and <0.1, respectively. When S.maltophilia has applied alone, the NorBC and NosZ were undetected, and denitrification was incomplete. The DsrA of S.maltophilia could produce sulfide as an alternative electron donor for T.denitrificans. Even though T.denitrificans had complete denitrification genes, its efficiency was low when used alone. The interaction of T.denitrificans and S.maltophilia reduced nitrite accumulation, leading to complete denitrification. A sufficient quantity of S.maltophilia may trigger the autotrophic denitrification activity of T.denitrificans. When the colony-forming units (CFU) ratio of S.maltophilia to T.denitrificans was reached at 2:1, the highest denitrification performance was achieved at 2.56 and 12.59 times higher than applied alone. This research provides a good understanding of the optimal microbial matching for the future application of bio-S.

Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma.

BACKGROUND: BRD4, belonging to the bromodomain extra-terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. METHODS: The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4-depleted AM cells, RNA sequencing (RNA-seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET-inhibitors (BETi) was assessed with AM patient-derived organoids. RESULTS: Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient-derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness-associated pathways. CONCLUSION: BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness-associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.

Compression of the Pulmonary Artery and Coronary Artery Caused by Pulmonary Epithelioid Hemangioendothelioma: A Case Report.

A 63-year-old woman with a five-month history of pulmonary epithelioid hemangioendothelioma (PEH) presented to the emergency department, due to worsening dyspnea and chest pain. The electrocardiography showed a pattern of ST-segment elevation in leads I, AVL, and poor R-wave progression consistent with anterolateral ischemia. Emergent coronary angiography revealed severe stenosis of the left main coronary artery. Then, contrast-enhanced computed tomography scan indicated the right pulmonary artery and left main coronary artery narrowing by compression of metastasized PEH. Finally, the patient died of deteriorated multi-organ failure.

A network analysis of positive developmental assets of Hong Kong school-age children during the Covid-19 pandemic.

The ongoing COVID19 pandemic is having detrimental effects on the mental and emotional well-being of many adults and children. It is relevant therefore to explore the combination of personal strengths and attributes that can help an individual develop resilience to such stress. Little is known about how psychological strength assets such as social connectedness, grit, hope, life meaning, and life satisfaction are inter-related, and if certain factors play a central role. This study involved a sample of 1,405 school-aged children in Hong Kong (50% female) from seven schools that participated in an online survey of psychological strengths. Data were analyzed by constructing a psychological network that found strength factors are inter-connected, and that 'school connectedness' and 'agency thinking' are central to the network. The information gained can be of value in any schools that are planning to provide strength-based interventions to help students maintain their psychological well-being during and after the COVID-19 pandemic.

Nidogen-2 Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells and Prevents Neointima Formation via Bridging Jagged1-Notch3 Signaling.

BACKGROUND: How the extracellular matrix (ECM) microenvironment modulates the contractile phenotype of vascular smooth muscle cells (VSMCs) and confers vascular homeostasis remains elusive. METHODS: To explore the key ECM proteins in the maintenance of the contractile phenotype of VSMCs, we applied protein-protein interaction network analysis to explore novel ECM proteins associated with the VSMC phenotype. By combining in vitro and in vivo genetic mice vascular injury models, we identified nidogen-2, a basement membrane glycoprotein, as a key ECM protein for maintenance of vascular smooth muscle cell identity. RESULTS: We collected a VSMC phenotype-related gene dataset by using Gene Ontology annotation combined with a literature search. A computational analysis of protein-protein interactions between ECM protein genes and the genes from the VSMC phenotype-related gene dataset revealed the candidate gene nidogen-2, a basement membrane glycoprotein involved in regulation of the VSMC phenotype. Indeed, nidogen-2-deficient VSMCs exhibited loss of contractile phenotype in vitro, and compared with wild-type mice, nidogen-2-/- mice showed aggravated post-wire injury neointima formation of carotid arteries. Further bioinformatics analysis, coimmunoprecipitation assays, and luciferase assays revealed that nidogen-2 specifically interacted with Jagged1, a conventional Notch ligand. Nidogen-2 maintained the VSMC contractile phenotype via Jagged1-Notch3 signaling but not Notch1 or Notch2 signaling. Nidogen-2 enhanced Jagged1 and Notch3 interaction and subsequent Notch3 activation. Reciprocally, Jagged1 and Notch3 interaction, signaling activation, and Jagged1-triggered VSMC differentiation were significantly repressed in nidogen-2-deficient VSMCs. In accordance, the suppressive effect of Jagged1 overexpression on neointima formation was attenuated in nidogen-2-/- mice compared with wild-type mice. CONCLUSIONS: Nidogen-2 maintains the contractile phenotype of VSMCs through Jagged1-Notch3 signaling in vitro and in vivo. Nidogen-2 is required for Jagged1-Notch3 signaling.

Next-generation sequencing reveals the mitogenomic heteroplasmy in the topmouth culter (Culter alburnus Basilewsky, 1855).

BACKGROUND: The mitogenomic heteroplasmy is the presence of multiple haplotypes in the mitochondria, which could cause genetic diseases and is also associated with many critical biological functions. The topmouth culter (Culter alburnus Basilewsky, 1855) is one of the most important freshwater fish in the family of Cyprinidae in China. At present, there are no reports on the topmouth culter's mtDNA heteroplasmy and the existence of which is not known. METHODS AND RESULTS: This study aimed to analyze the mitogenomic heteroplasmy in the topmouth culter by the next-generation sequencing of the fins' total DNA. The results confirmed the existence of the heteroplasmy and indicated the presence of the extensive heteroplasmy in the topmouth culter's mitogenome. There were 38 heteroplasmic variations in the protein-coding genes from the three specimens, with 33 non-synonymous substitutions accounting for 86.84% and five synonymous substitutions accounting for 13.16%. Among them, the ND6 had the most heteroplasmic variations but only one synonymous substitution. After removing the putative nuclear mitochondrial DNA fragments, the ratio of primary haplotype in the three specimens was 43.89%, 74.72%, and 32.76%, respectively. The three specimens contained 21, 7, and 21 haplotypes of the mitogenomes, respectively. Due to the extensive heteroplasmy, we reconstructed the phylogenetic tree of the topmouth culter using the RY-coding method, which improved the performance of the phylogenetic tree to some extent. CONCLUSIONS: This study reported the mitogenomic heteroplasmy in the topmouth culter and enhanced the knowledge regarding the mitogenomic heteroplasmy in phylogenetic studies. As the topmouth culter is a commercial species, the mitogenomic heteroplasmy is crucial for the fisheries management of the topmouth culter.

Prognostic and clinicopathological significance of cytocapsular tubes in oral squamous cell carcinoma.

BACKGROUND: Cytocapsular tubes (CTs) provide membranous channels for cancer cells interconnection and multidirectional locomotion, which facilitate cancer cell transportation and metastasis. However, the clinicopathological significance of CTs has not been documented in oral squamous cell carcinoma (OSCC). Herein, we aimed to identify CTs and assess their clinicopathological significance in OSCC. METHODS: Operetta CLS™ high-content analysis system was used to detect the CTs originated from OSCC cells cultured in a 3D Matrigel matrix. Then, pan-cadherin and γ-actin immunostaining were performed to identify CTs in 4NQO-induced murine OSCC tissues, OSCC xenografts and 88 human primary OSCC samples. Finally, the prognostic value and clinicopathological significance of CTs in OSCC were further examined by using the Kaplan-Meier method and Cox regression analysis. RESULTS: CTs were observed in OSCC cells in a 3D Matrigel matrix. In vivo, CTs were frequently identified in 4NQO-induced murine OSCC tissues, OSCC xenografts and human primary OSCC samples. CTs density was significantly associated with T stage, lymph node metastasis, differentiation, invasive depth, tumor budding, TNM stage and tumor recurrence. Importantly, the high-CTs density indicated a decreased overall survival (OS) and progression-free survival (PFS) in OSCC patients. Cox regression models showed that CTs could serve as a prognostic factor for OS and PFS. CONCLUSION: CTs, which are correlated with the cell migration and invasion, can be readily identified in OSCC and appear to be a novel biomarker for patients at risk of metastasis.

FOSL1 promotes metastasis of head and neck squamous cell carcinoma through super-enhancer-driven transcription program.

Previously, we discovered that FOSL1 facilitates the metastasis of head and neck squamous cell carcinoma (HNSCC) cancer stem cells in a spontaneous mouse model. However, the molecular mechanisms remained unclear. Here, we demonstrated that FOSL1 serves as the dominant activating protein 1 (AP1) family member and is significantly upregulated in HNSCC tumor tissues and correlated with metastasis of HNSCC. Mechanistically, FOSL1 exerts its function in promoting tumorigenicity and metastasis predominantly via selective association with Mediators to establish super-enhancers (SEs) at a cohort of cancer stemness and pro-metastatic genes, such as SNAI2 and FOSL1 itself. Depletion of FOSL1 led to disruption of SEs and expression inhibition of these key oncogenes, which resulted in the suppression of tumor initiation and metastasis. We also revealed that the abundance of FOSL1 is positively associated with the abundance of SNAI2 in HNSCC and the high expression levels of FOSL1 and SNAI2 are associated with short overall disease-free survival. Finally, the administration of the FOSL1 inhibitor SR11302 significantly suppressed tumor growth and lymph node metastasis of HNSCC in a patient-derived xenograft model. These findings indicate that FOSL1 is a master regulator that promotes the metastasis of HNSCC through a SE-driven transcription program that may represent an attractive target for therapeutic interventions.

The systemic inflammation response index predicts the survival of patients with clinical T1-2N0 oral squamous cell carcinoma.

OBJECTIVE: The systemic inflammation response index (SIRI) is an independent prognostic factor for many malignant tumors. However, the value of this factor in patients with clinical T1-2N0 (cT1-2N0) oral squamous cell carcinoma (OSCC) is still unclear. METHODS: We calculated SIRI of 235 cT1-2N0 OSCC patients from 2013 to 2017. Multivariate cox regression analysis was applied to verify the prognostic significance of SIRI. Kaplan-Meier curves were plotted to analyze the overall survival (OS) and disease-specific survival (DSS) for cT1-2N0 OSCC patients. RESULTS: According to the optimal cutoff point of SIRI, we divided cT1-2N0 OSCC patients into high SIRI group (SIRI ≥ 1.3) and low SIRI group (SIRI < 1.3). SIRI was an independent prognostic indicator for OS (HR = 2.87; 95% CI = 1.35-6.10; p = .006) and DSS (HR = 2.17; 95% CI = 1.10-4.27; p = .025). High SIRI had a significantly poorer OS (p = .001) and DSS (p = .007) in survival analysis than the low SIRI. Moreover, the prognostic value of SIRI was significantly stronger than neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR). CONCLUSIONS: Preoperative SIRI can be regarded as a meaningful indicator for poor survival of cT1-2N0 OSCC patients, and it is a promising tool to formulate the best individualized treatment for high-risk patients.

Baseline assessment of enhanced recovery after pediatric surgery in mainland China.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a clinical pathway that optimizes perioperative management based on evidence-based medicine. ERAS has been gradually introduced to pediatric surgery in recent years. However, there are limited reports on its overall implementation. We aimed to determine the implementation of ERAS in patients who received pediatric surgery in mainland China. METHODS: We designed a questionnaire involving 17 key ERAS elements and sent the questionnaire to 66 chiefs of pediatric surgery distributed throughout 31 provinces in mainland China to obtain a baseline assessment of the assimilation of ERAS protocols in the care of congenital biliary dilatation (CBD). RESULTS: A total of 66 questionnaires were collected. The range of elements implemented at participating centers was 4-16, with a mean of 10.23. The least commonly practiced elements were administration of non-opioid preoperative analgesia (6 centers, 9.09%), prevention of postoperative nausea and vomiting [PONV] (9 centers, 13.64%), and postoperative pain management (26 centers, 39.39%). CONCLUSIONS: The implementation of elements differed from center to center. Measures relying primarily on anesthesiologists had lower execution. The adherence to ERAS elements was often inhibited by a lack of institutional support, poor knowledge of ERAS protocols, and difficulties in coordinating multidisciplinary care, as well intransigence in changing surgical practices out of fear of liability for poor outcomes.