Two-dimensional quantum universality in the spin-1/2 triangular-lattice quantum antiferromagnet Na2BaCo(PO4)2.

An interplay of geometrical frustration and strong quantum fluctuations in a spin-1/2 triangular-lattice antiferromagnet (TAF) can lead to exotic quantum states. Here, we report the neutron-scattering, magnetization, specific heat, and magnetocaloric studies of the recently discovered spin-1/2 TAF Na2BaCo(PO4)2, which can be described by a spin-1/2 easy axis XXZ model. The zero-field neutron diffraction experiment reveals an incommensurate antiferromagnetic ground state with a significantly reduced ordered moment of about 0.54(2) µB/Co. Different magnetic phase diagrams with magnetic fields in the ab plane and along the easy c-axis were extracted based on the magnetic susceptibility, specific heat, and elastic neutron-scattering results. In addition, two-dimensional (2D) spin dispersion in the triangular plane was observed in the high-field polarized state, and microscopic exchange parameters of the spin Hamiltonian have been determined through the linear spin wave theory. Consistently, quantum critical behaviors with the universality class of d = 2 and νz = 1 were established in the vicinity of the saturation field, where a Bose-Einstein condensation (BEC) of diluted magnons occurs. The newly discovered quantum criticality and fractional magnetization phase in this ideal spin-1/2 TAF present exciting opportunities for exploring exotic quantum phenomena.

N6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X.

BACKGROUND: Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS: The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS: We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS: Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.

Perceived social support mediates cancer and living meaningfully intervention effects on quality of life after breast cancer surgery.

Aim: To explore the role of perceived social support in enhancing psychological resilience and quality of life in postoperative breast cancer patients. Materials & methods: The Managing Cancer and Living Meaningfully (CALM) intervention was used to improve indicators such as psychological resilience in breast cancer patients, while the role of perceived social support in this was assessed. Results: The intervention group exhibited significant improvements compared with the control group in psychological resilience (F = 9.059, p < 0.01). The analysis showed that increased social support in the control group partly mediated the link between psychological resilience and quality of life. Conclusion: CALM improves overall well-being, indicating that incorporating it into standard care for post-mastectomy patients can positively impact their mental health.

[Box: see text].

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

A Predictive Model for the Early Death of Breast Cancer With Synchronous Liver Metastases: A Population-Based Study.

BACKGROUND: Breast cancer liver metastasis (BCLM) is a severe condition often resulting in early death. The identification of prognostic factors and the construction of accurate predictive models can guide clinical decision-making. METHODS: A large sample of data from the Surveillance, Epidemiology, and End Results (SEER) database was analyzed, including 3711 patients diagnosed with de novo BCLM between 2010 and 2015. Predictive models were developed using histograms, and stepwise regression addressed variable collinearity. Internal validation was performed, and results were compared to similar studies. RESULTS: In this study of 3711 BCLM patients, 2571 didn't have early death. Out of the 1164 who died early, 1086 had cancer-specific early death. Prognostic factors for early death, including age, race, tumor size, and lymph node involvement, were identified. A nomogram based on these factors was constructed, accurately predicting early all-cause and cancer-specific death. CONCLUSIONS: Valuable insights into the prognosis of BCLM patients were provided, and important prognostic factors for early death were identified. The developed nomogram can assist clinicians in identifying high-risk patients for early death and inform treatment decisions.

Shift work and nonalcoholic fatty liver disease incidence among Chinese rail workers: a 4-year longitudinal cohort study.

PURPOSE: Occupational harmful factors, such as shift work, are attracting increasing attention as a potential cause of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to identify the association between shift work and NAFLD incidence in Chinese rail population. METHODS: A cohort study was conducted among 14,112 rail workers for 4-year follow-up. Shift work frequency and other potential variables were recorded by questionnaires, including demographic, lifestyle, and occupation information. Besides, body mass index, blood pressure, fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase were measured by anthropometric measurement and blood test. Diagnosis of new NAFLD case was based on abdominal ultrasonography. Cox proportional hazards regression model was used to determine whether shift work has effect on occurrence of NAFLD. RESULTS: The incidence of NAFLD was 30.43% in total subjects. After adjustment for possible confounders, the RRs of NAFLD were 1.069 (95% CI 0.998-1.146) and 1.179 (95% CI 1.059-1.312) in occasionally shift work group and frequently shift work group respectively, compared to the seldom shift work group. In stratified analyses, the RRs of NAFLD incidence linked to shift work exposure seems increase among female and elder. The results of three sensitivity analyses were similar with main analysis. CONCLUSIONS: This research provided further evidence of positive harmful effect of shift work on NAFLD incidence in Chinese rail workers, particularly in frequently shift work population. The risk estimate of shift work on NAFLD was higher in female and elder.

H3K27 acetylation activated-CD109 evokes 5-fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway.

Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5-fluorouracil (5-FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5-FU-resistant GC cells. CD109 deficiency lessened the IC50 value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5-FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5-FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation-induced changes of IC50 values, cell viability, metastasis and apoptosis in NCI-N87/5-FU and SNU-1/5-FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated-CD109 enhanced 5-FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC.

Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study.

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS: This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Pharmacological inhibition of CDK7 by THZ1 impairs tumor growth in p53-mutated HNSCC.

BACKGROUND: Cyclin-dependent kinase 7 (CDK7) has been critically linked to human cancer. However, the roles of CDK7 in head and neck squamous cell carcinoma (HNSCC) remain incompletely known. Here, we sought to dissect the functions of CDK7 underlying HNSCC tumorigenesis and explore whether pharmacological inhibition of CDK7 could induce anti-cancer effects. METHODS: CDK7 expression was measured in a panel of HNSCC cell lines with p53 mutation and 20 pairs of HNSCC samples and adjacent non-tumor tissues. Genetic targeting and pharmacological inhibition of CDK7 were conducted to dissect the biological roles of CDK7 in p53-mutated HNSCC cells. An HNSCC xenograft model was developed to determine the therapeutic effects of THZ1 in vivo. Potential genes and pathways responsible for therapeutic effects of THZ1 were identified by genome-wide RNA-sequencing and bioinformatics interrogations. RESULTS: CDK7 expression was significantly elevated in cancerous cells and samples as compared with their adjacent non-tumor counterparts. Impaired cell proliferation, migration, and invasion as well increased apoptosis were observed in cells upon CDK7 knockdown or THZ1 exposure. THZ1 administration potently inhibited tumor overgrowth in vivo. Mechanistically, hundreds of genes enriched in cell proliferation, apoptosis, and cancer-related categories were identified to be potentially mediated the therapeutic effects of THZ1 in HNSCC. CONCLUSION: Our findings reveal that CDK7 might serve as a novel putative pro-oncogenic gene underlying HNSCC tumorigenesis and therapeutic targeting of CDK7 might be a promising strategy for p53-mutated HNSCC.

Long-term PM2.5 exposure in association with chronic respiratory diseases morbidity: A cohort study in Northern China.

Several literatures have examined the risk of chronic respiratory diseases in association with short-term ambient PM2.5 exposure in China. However, little evidence has examined the chronic impacts of PM2.5 exposure on morbidity of chronic respiratory diseases in cohorts from high pollution countries. Our study aims to investigate the associations. Based on a retrospective cohort among adults in northern China, a Cox regression model with time-varying PM2.5 exposure and a concentration-response (C-R) curve model were performed to access the relationships between incidence of chronic respiratory diseases and long-term PM2.5 exposure during a mean follow-up time of 9.8 years. Individual annual average PM2.5 estimates were obtained from a satellite-based model with high resolution. The incident date of a chronic respiratory disease was identified according to self-reported physician diagnosis time and/or intake of medication for treatment. Among 38,047 urban subjects analyzed in all-cause chronic respiratory disease cohort, 482 developed new cases. In CB (38,369), asthma (38,783), and COPD (38,921) cohorts, the onsets were 276, 89, and 14, respectively. After multivariable adjustment, hazard ratio and 95% confidence interval for morbidity of all-cause chronic respiratory disease, CB, asthma, and COPD were 1.15 (1.01, 1.31), 1.20 (1.00, 1.42), 0.76 (0.55, 1.04), and 0.66 (0.29, 1.47) with each 10 µg/m3 increment in PM2.5, respectively. Stronger effect estimates were suggested in alcohol drinkers across stratified analyses. Additionally, the shape of C-R curve showed an increasing linear relationship before 75.00 µg/m3 concentrations of PM2.5 for new-onset all-cause chronic respiratory disease, and leveled off at higher levels. These findings indicated that long-term exposure to high-level PM2.5 increased the risks of incident chronic respiratory diseases in China. Further evidence of C-R curves is warranted to clarify the associations of adverse chronic respiratory outcomes involving air pollution.

Comprehensive characterization of epidemiological and 3D radiographic features of non-third molar impacted teeth in a Chinese dental population.

OBJECTIVE: This retrospective study aimed to comprehensively delineate the epidemiological and 3-dimensional radiographic characteristics of non-third molar (non-M3) impacted teeth in a Chinese dental population. MATERIAL AND METHODS: Patients with impacted teeth except for the third molar (ITEM3) were retrospectively screened via cone-beam CT images from 75,021 patients treated at our institution from June 2012 to December 2018. Demographic and clinical data of patients with ITEM3 were retrieved from medical records. CBCT coupled with 3-dimensional reconstruction was employed to characterize the radiographic features of ITEM3. Associations between these epidemiological, clinical, and radiographic features were further statistically analyzed. RESULTS: Among 1975 eligible patients, 2467 ITEM3s were identified with a prevalence of 2.63% (1975/75,021). Females slightly outnumbered males with a ratio of 1.12:1. The majority of ITEM3 was single (1577, 79.85%) in the maxilla. The maxillary canine teeth were the most frequently impacted (52.45%), followed by maxillary incisors. The mesioangular position was the most common orientation (43.8%), followed by vertical and buccal-lingual orientations. The most frequently associated lesion was external root resorption of the adjacent tooth, which was significantly correlated with the morphology and position of the impacted tooth. CONCLUSION: Most ITEM3 was single, mesioangular, found at maxillary canines, sometimes associated with diverse complications. Our data advance the current understanding of ITEM3 and offer insights into the management of this dental abnormality. CLINICAL RELEVANCE: These findings are useful for clinicians to comprehensively understand the prevalence, radiographic features, and complications of non-M3 impacted teeth.

Sulfur [18F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis.

The lack of efficient [18F]fluorination processes and target-specific organofluorine chemotypes remains the major challenge of fluorine-18 positron emission tomography (PET). We report here an ultrafast isotopic exchange method for the radiosynthesis of novel PET agent aryl [18F]fluorosulfate enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully automated 18F-radiolabeling of 25 structurally and functionally diverse aryl fluorosulfates with excellent radiochemical yield (83-100%, median 98%) and high molar activity (280 GBq µmol-1) at room temperature in 30 s. The purification of radiotracers requires no time-consuming HPLC but rather a simple cartridge filtration. We further demonstrate the imaging application of a rationally designed poly(ADP-ribose) polymerase 1 (PARP1)-targeting aryl [18F]fluorosulfate by probing subcutaneous tumors in vivo.

Identification of an autophagy-related prognostic signature in head and neck squamous cell carcinoma.

BACKGROUND: Autophagy-related genes (ARGs) have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop an ARGs-based prognostic signature for Head and neck squamous cell carcinoma (HNSCC). METHODS: Prognostic ARG candidates were identified by univariate and multivariate Cox regression analysis in the training dataset (TCGA-HNSC) and incorporated into a 3-ARGs (EGFR, FADD, and PARK2) prognostic signature which was further verified in two independent validation cohorts (GSE41613 and GSE42743). Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristics curves (ROC) were employed to evaluate the prognostic prediction of 3-ARGs signature. Differential expression of these 3 ARG between cancer and normal counterparts as well as their associations with autophagy markers were assessed in 60 pairs of freshly collected HNSCC and adjacent non-tumor samples and datasets from Human Protein Atlas, respectively. RESULTS: Patients with high-risk score had significantly inferior overall survival. Multivariate regression analyses revealed that 3-ARGs signature could be an independent prognostic factor after adjusting various clinicopathological parameters. ROC analyses revealed high predictive accuracy and sensitivity of the 3-ARGs signature. Increased mRNA and protein expression of EGFR, FADD, and PARK2 were found in HNSCC samples, and their expression significantly correlated with the abundances of ATG5, Beclin1, and LC3. CONCLUSION: Our results reveal that 3-ARGs signature is a powerful prognostic biomarker for HNSCC, which could be integrated into the current prognostic regime to realize individualized outcome prediction. EGFR, FADD, and PARK2 likely contributed to autophagy during HNSCC tumorigenesis.

Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. DATA SOURCES: PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. STUDY SELECTION: Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. DATA EXTRACTION: Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. CONCLUSIONS: BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.

Epidemiological, clinical, radiographic characterization of non-syndromic supernumerary teeth in Chinese children and adolescents.

OBJECTIVE: This retrospective study was purposed to evaluate epidemiological, clinical, and 3D radiological features of supernumerary teeth (ST) in a non-syndromic Chinese children and adolescent dental population. MATERIALS AND METHODS: Original cone-beam CT (CBCT) data from 18,861 patients aged from 6 to 17 years with dental maxillofacial diseases treated in a Chinese dental hospital from June 2012 to December 2018 were utilized to screen patients with ST. Diagnosis and characterizations of ST were analyzed by CBCT coupled with 3D reconstruction. All relevant epidemiological, clinical, and radiographic details about ST were collected and statistically analyzed. RESULTS: Among total 18,861 patients, 2,768 ST were identified in 1984 subjects with a prevalence of 10.52% and a male:female ratio of 1.86:1. Majority of ST were single, conical, inverted, impacted, and located in maxilla anterior region. ST-associated complications mainly included malposition, rotation, and impaction of adjacent teeth, which were notably associated with morphology and position of ST. CONCLUSION: The prevalence of ST in Chinese children and adolescent dental population was 10.52% and tended to present as single, conical, inverted, and impacted, which resulted in abnormalities of neighboring teeth. Our outcomes are beneficial for clinicians to more comprehensively understand the incidence, characterization, and clinical treatment planning of ST in dental children and adolescents.

Serum tRNA-derived fragments (tRFs) as potential candidates for diagnosis of nontriple negative breast cancer.

Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non-TNBC) accounts for 80-90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA-derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high-throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non-TNBC. Furthermore, quantitative reverse-transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR-7816, tDR-5334, and tDR-4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR-7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR-7816 expression as a novel potential biomarker for the diagnosis of patients with early non-TNBC.

Predictive value of prognostic nutritional index in patients with oral squamous cell carcinoma.

OBJECTIVES: To determine the prognostic significance of preoperative prognostic nutritional index (PNI) in patients with primary oral squamous cell carcinoma (OSCC) after ablative surgery. MATERIALS AND METHODS: A total of 333 patients from two tertiary referral centers were enrolled as training and validation cohorts. The PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte number (per mm3 ), and its optimal cutoff value for patient stratification was identified by X-tile software. Cox's proportional regression analyses and receiver operating characteristic (ROC) curves were employed to identify prognostic factors and their predictive performance. RESULTS: The optimal cutoff value of PNI was 47.4. Patients with low PNI had significantly shorter overall (OS) and disease-free survival than those with high PNI. Moreover, multivariate regression analyses indicated that PNI was an independent prognostic factor for OS in the training (hazard ratio [HR], 2.267; 95% confidence interval [CI]:1.335-3.849; p = .002) and validation (HR, 2.247; 95% CI: 1.352-3.735; p = .002) cohorts. ROC analyses revealed similar or superior predictive performance of PNI as compared to other prognostic parameters. CONCLUSIONS: Our findings reveal that decreased preoperative PNI significantly associates with worse prognosis for patients with OSCC, which serves as a novel prognostic biomarker for OSCC.

Overexpression of ZEB2-AS1 promotes epithelial-to-mesenchymal transition and metastasis by stabilizing ZEB2 mRNA in head neck squamous cell carcinoma.

The long noncoding RNAs (lncRNAs) have been increasingly appreciated as key players underlying tumourigenesis and hold great potentials as prognostic biomarkers and therapeutic targets. However, their roles in head neck squamous cell carcinoma (HNSCC) have remained incompletely known. Here, we sought to reveal the oncogenic roles and clinical significance of a tumour-associated lncRNA, zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), in HNSCC. ZEB2-AS1 was aberrantly overexpressed in a fraction of HNSCC samples. Its overexpression significantly associated with large tumour size, cervical node metastasis and reduced overall and disease-free survival. Antisense oligonucleotides (ASO)-mediated ZEB2-AS1 depletion markedly inhibited cell proliferation, migration and invasion while triggered apoptosis in HNSCC cells in part via modulating ZEB2 mRNA stability. Enforced overexpression of ZEB2 largely attenuated the phenotypic changes resulted from ZEB2-AS1 inhibition except the impaired cell proliferation. In addition, ZEB2-AS1 was required for TGF-ß1-induced epithelial-mesenchymal transition (EMT) in vitro. Significantly reduced tumour growth and lung metastasis were observed in ZEB2-AS1-depleted cells in HNSCC xenograft animal models. Taken together, our findings reveal that overexpression of ZEB2-AS1 associates with tumour aggressiveness and unfavourable prognosis by serving as a putative oncogenic lncRNA and a novel prognostic biomarker in HNSCC.

Hypoxia-induced tRNA-derived fragments, novel regulatory factor for doxorubicin resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA-derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia-treated TNBC cell lines through the use of high-throughput sequencing technique. Quantitative real-time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR-0009 [derived from transfer RNA (tRNA)Gly-GCC-1-1 ] and tDR-7336 (derived from tRNA Gly-GCC-1-2 ) were significantly upregulated when the SUM-1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)-6, which may be the underlying mechanism of hypoxia-induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein-protein interaction network for predicted target genes established by the STRING database manifested that tDR-0009 (tDR-7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia-treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia-induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets.

Identification of 4-lncRNA prognostic signature in head and neck squamous cell carcinoma.

Deregulated long noncoding RNAs (lncRNA) have been critically implicated in tumorigenesis and serve as novel diagnostic and prognostic biomarkers. Here we sought to develop a prognostic lncRNA signature in patients with head and neck squamous cell carcinoma (HNSCC). Original RNA-seq data of 499 HNSCC samples were retrieved from The Cancer Genome Atlas database, which was randomly divided into training and testing set. Univariate Cox regression survival analysis, robust likelihood-based survival model and random sampling iterations were applied to identify prognostic lncRNA candidates in the training cohort. A prognostic risk score was developed based on the Cox coefficient of four individual lncRNA imputed as follows: (0.14546 × expression level of RP11-366H4.1) + (0.27106 × expression level of LINC01123) + (0.54316 × expression level of RP11-110I1.14) + (-0.48794 × expression level of CTD-2506J14.1). Kaplan-Meier analysis revealed that patients with high-risk score had significantly reduced overall survival as compared with those with low-risk score when patients in training, testing, and validation cohorts were stratified into high- or low-risk subgroups. Multivariate survival analysis further revealed that this 4-lncRNA signature was a novel and important prognostic factor independent of multiple clinicopathological parameters. Importantly, ROC analyses indicated that predictive accuracy and sensitivity of this 4-lncRNA signature outperformed those previously well-established prognostic factors. Noticeably, prognostic score based on quantification of these 4-lncRNA via qRT-PCR in another independent HNSCC cohort robustly stratified patients into subgroups with high or low survival. Taken together, we developed a robust 4-lncRNA prognostic signature for HNSCC that might provide a novel powerful prognostic biomarker for precision oncology.