Euchromatin histone-lysine N-methyltransferase 2 regulates the expression of potassium-sodium-activated channel subfamily T member 1 in primary sensory neurons and contributes to remifentanil-induced pain sensitivity.

Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2/G9a) in neuropathic pain associated with the transcriptional silencing of many potassium ion channel genes. This study investigates whether G9a regulates the potassium sodium-activated channel subfamily T member 1 (Slo2.2) in remifentanil-induced post-incisional hyperalgesia (RIH) in rodents. We performed remifentanil infusion (1 µg·kg-1·min-1 for 60 min) followed by plantar incision to induce RIH in rodents. Our results showed that RIH was accompanied by increased G9a and H3K9me2 production and decreased Slo2.2 expression 48 h postoperatively. Deletion of G9a rescued Slo2.2 expression in DRG and reduced RIH intensity. Slo2.2 overexpression also reversed this hyperalgesia phenotype. G9a overexpression decreased Slo2.2-mediated leak current and increased excitability in the small-diameter DRG neurons and laminal II small-diameter neurons in the spinal dorsal horn, which was implicated in peripheral and central sensitization. These results suggest that G9a contributes to the development of RIH by epigenetically silencing Slo2.2 in DRG neurons, leading to decreased central sensitization in the spinal cord. The findings may have implications for the development of novel therapeutic targets for the treatment of postoperative pain.

Quantitative Assessment of Hemodynamics Associated With Embolization Degree in Brain Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes. METHODS: We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes. RESULTS: Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001). CONCLUSION: Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.

Carbon ecological security assessment based on the decoupling relationship between carbon balance pressure and ecological quality in Xuzhou City, China.

Building a carbon ecological security (CES) framework helps to scientifically evaluate and manage the regional carbon cycle and eco-environment and support regional ecological security patterns. This paper adopted the pressure-state-response-immune (PSRI) model and the carbon balance index method to evaluate the ecological quality and carbon balance pressure. Then, based on the decoupling model and the improved four-quadrant model, the CES framework was constructed to evaluate the changing trend of the CES of Xuzhou City from 2005 to 2020. The results showed that the carbon balance pressure of Xuzhou City showed a pattern of "low-high-low" from east to west, and most areas tended to have a carbon balance and surplus in 2020. The ecological quality showed an overall upward trend during the study period. Protection and restoration drove the response and immune index growth from 2010 to 2020. In the Thirteenth Five-Year Plan stage, the nine districts of Xuzhou City were in a stable decoupling state, and the overall decoupling process was ideal. The CES of districts showed individual differences in the general upward trend. The carbon balance pressure of Gulou and Quanshan Districts was the main factor restricting the districts' CES. Therefore, based on the empirical results, this research proposes relevant suggestions to enhance carbon ecological security to achieve regional green and low-carbon development.

How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

Exploring patient medication adherence and data mining methods in clinical big data: A contemporary review.

BACKGROUND: Increasingly, patient medication adherence data are being consolidated from claims databases and electronic health records (EHRs). Such databases offer an indirect avenue to gauge medication adherence in our data-rich healthcare milieu. The surge in data accessibility, coupled with the pressing need for its conversion to actionable insights, has spotlighted data mining, with machine learning (ML) emerging as a pivotal technique. Nonadherence poses heightened health risks and escalates medical costs. This paper elucidates the synergistic interaction between medical database mining for medication adherence and the role of ML in fostering knowledge discovery. METHODS: We conducted a comprehensive review of EHR applications in the realm of medication adherence, leveraging ML techniques. We expounded on the evolution and structure of medical databases pertinent to medication adherence and harnessed both supervised and unsupervised ML paradigms to delve into adherence and its ramifications. RESULTS: Our study underscores the applications of medical databases and ML, encompassing both supervised and unsupervised learning, for medication adherence in clinical big data. Databases like SEER and NHANES, often underutilized due to their intricacies, have gained prominence. Employing ML to excavate patient medication logs from these databases facilitates adherence analysis. Such findings are pivotal for clinical decision-making, risk stratification, and scholarly pursuits, aiming to elevate healthcare quality. CONCLUSION: Advanced data mining in the era of big data has revolutionized medication adherence research, thereby enhancing patient care. Emphasizing bespoke interventions and research could herald transformative shifts in therapeutic modalities.

Morphology evolution of the aluminum surface in a fluorine-containing environment.

The interaction between aluminum (Al) and F and O atoms is essential to understand the etching process of Al and alumina (Al2O3) by fluorine-containing gases. In addition, it also has an influence on the corrosion behavior of Al devices, e.g., the Al collector in lithium-ion batteries operates in fluorine-containing electrolytes. However, the understanding of the structural evolution of the Al surface by fluorination at the atomistic level still remains elusive. Here, the thermodynamic and kinetic behaviors of F adatoms as well as co-adsorbed F and O adatoms on typical Al surfaces have been systematically investigated by combining density functional theory (DFT) calculations, canonical Monte Carlo (CMC) simulations and reactive molecular dynamics (RMD) simulations. The results of DFT calculations indicate that there is a repulsion (about 0.07 eV on Al(111) and Al(110), and 0.7 eV on Al(100)) between the first nearest neighboring (1NN) F adatoms, while an attraction of 0.14 eV on Al(111) exists within a 1NN F-O pair. CMC simulations reveal that the configurations of co-adsorbed F and O adatoms on the Al(111) surface at medium to low temperature (<600 K) and low total coverage (<0.2 monolayer, ML) have F adatoms dispersed in the hexagonal islands of O adatoms due to the attraction within the O-O and F-O pairs and the repulsion between F adatoms. As the coverage increases, the surface undergoes serious deformation. The average 1NN coordination numbers (1st CN) of O-to-O, F-to-O and F-to-F are six, three and zero, respectively. As the temperature increases, the interactions among adsorbates begin to be disrupted: the 1st CNs of O-to-O and F-to-O decrease, while that of F-to-F increases. The O-F hexagonal pattern remains until above the Al melting temperature (>1200 K). For F adatoms, both their migration on the surface and the penetration into the subsurface are easier than those of O adatoms, confirmed by both the DFT and RMD simulations. Our study on the co-adsorbates with opposite lateral interactions is instructive for understanding the thermal etching of Al and Al2O3 by fluorine-containing compounds.

Interspecific differences in thermal tolerance landscape explain aphid community abundance under climate change.

A single critical thermal limit is often used to explain and infer the impact of climate change on geographic range and population abundance. However, it has limited application in describing the temporal dynamic and cumulative impacts of extreme temperatures. Here, we used a thermal tolerance landscape approach to address the impacts of extreme thermal events on the survival of co-existing aphid species (Metopolophium dirhodum, Sitobion avenae and Rhopalosiphum padi). Specifically, we built the thermal death time (TDT) models based on detailed survival datasets of three aphid species with three ages across a broad range of stressful high (34-40 °C) and low (-3∼-11 °C) temperatures to compare the interspecific and developmental stage variations in thermal tolerance. Using these TDT parameters, we performed a thermal risk assessment by calculating the potential daily thermal injury accumulation associated with the regional temperature variations in three wheat-growing sites along a latitude gradient. Results showed that M. dirhodum was the most vulnerable to heat but more tolerant to low temperatures than R. padi and S. avenae. R. padi survived better at high temperatures than Sitobion avenae and M. dirhodum but was sensitive to cold. R. padi was estimated to accumulate higher cold injury than the other two species during winter, while M. dirhodum accrued more heat injury during summer. The warmer site had higher risks of heat injury and the cooler site had higher risks of cold injury along a latitude gradient. These results support recent field observations that the proportion of R. padi increases with the increased frequency of heat waves. We also found that young nymphs generally had a lower thermal tolerance than old nymphs or adults. Our results provide a useful dataset and method for modelling and predicting the consequence of climate change on the population dynamics and community structure of small insects.

Effects of qCON and qNOX-guided general anaesthesia management on patient opioid use and prognosis: a study protocol.

INTRODUCTION: The adverse effects of general anaesthetic drugs (especially opioids) cannot be ignored. However, current nociceptive-monitoring techniques still lack consistency in guiding the use of opioids. This trial will study the demand for opioid use and patient prognosis in qCON and qNOX-guided general anaesthesia management. METHODS AND ANALYSIS: This prospective, randomised, controlled trial will randomly recruit 124 patients undergoing general anaesthesia for non-cardiac surgery in equal numbers to either the qCON or BIS group. The qCON group will adjust intraoperative propofol and remifentanil dosage according to qCON and qNOX values, while the BIS group will adjust according to BIS values and haemodynamic fluctuations. The differences between the two groups will be observed in remifentanil dosing and prognosis. The primary outcome will be intraoperative remifentanil use. Secondary outcomes will include propofol consumption; the predictive ability of BIS, qCON and qNOX on conscious responses, noxious stimulus and body movements; and changes in cognitive function at 90 days postoperatively. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2022-YX-075-01). Participants gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059877.

OsMADS17 simultaneously increases grain number and grain weight in rice.

During the processes of rice domestication and improvement, a trade-off effect between grain number and grain weight was a major obstacle for increasing yield. Here, we identify a critical gene COG1, encoding the transcription factor OsMADS17, with a 65-bp deletion in the 5' untranslated region (5' UTR) presented in cultivated rice increasing grain number and grain weight simultaneously through decreasing mRNA translation efficiency. OsMADS17 controls grain yield by regulating multiple genes and that the interaction with one of them, OsAP2-39, has been characterized. Besides, the expression of OsMADS17 is regulated by OsMADS1 directly. It indicates that OsMADS1-OsMADS17-OsAP2-39 participates in the regulatory network controlling grain yield, and downregulation of OsMADS17 or OsAP2-39 expression can further improve grain yield by simultaneously increasing grain number and grain weight. Our findings provide insights into understanding the molecular basis co-regulating rice yield-related traits, and offer a strategy for breeding higher-yielding rice varieties.

The interspecific variations in molecular responses to various doses of heat and cold stress: The case of cereal aphids.

Insects are currently subjected to unprecedented thermal stress due to recent increases in the frequency and amplitude of temperature extremes. Understanding molecular responses to thermal stress is critically important to appreciate how species react to thermal stress. Three co-occurring cosmopolitan species are found within the guild of cereal aphids: Sitobion avenae, Ropalosiphum padi and Metopolophium dirhodum. Earlier reports have shown that increasing frequency of temperature extremes causes a shift in dominant species within guilds of cereal aphids by differently altering the population's growth. We hypothesize that a differential molecular response to stress among species may partially explain these changes. Heat shock proteins (HSPs) are molecular chaperones well known to play an important role in protecting against the adverse effects of thermal stress. However, few studies on molecular chaperones have been conducted in cereal aphids. In this study, we compared the heat and cold tolerance between three aphid species by measuring the median lethal time (Lt50) and examined the expression profiles of seven hsp genes after exposures to comparable thermal injury levels and also after same exposure durations. Results showed that R. padi survived comparatively better at high temperatures than the two other species but was more cold-sensitive. Hsp genes were induced more strongly by heat than cold stress. Hsp70A was the most strongly up-regulated gene in response to both heat and cold stress. R. padi had more heat inducible genes and significantly higher mRNA levels of hsp70A, hsp10, hsp60 and hsp90 than the other two species. Hsps ceased to be expressed at 37 °C in M. dirhodum and S. avenae while expression was maintained in R. padi. In contrast, M. dirhodum was more cold tolerant and had more cold inducible genes than the others. These results confirm species-specific differences in molecular stress responses and suggest that differences in induced expression of hsps may be related to species' thermal tolerance, thus causing the changes in the relative abundance.

Coverage-dependent adsorption and dissociation of H2O on Al surfaces.

The adsorption and dissociation of H2O on Al surfaces including crystal planes and nanoparticles (ANPs) are systematically investigated by using density functional theory (DFT) calculations. H2O adsorption strength follows the order ANPs > Al(110) > Al(111) > Al(100). Due to the smaller cluster deformation caused by the moderate H2O adsorption, the relative magnitude of H2O adsorption strength on ANPs and crystal planes is opposite to the trend of adatoms like O* and/or N*. The energy barrier for the decomposition of H2O into H* and OH* is larger on ANPs than on crystal planes, and it decreases with the increasing cluster size. Due to the competition between the hydrogen (H) bonding among water molecules and the interaction between the water molecules and the substrate, the adsorption strength of H2O first increases and then decreases with the increase of water coverage. Moreover, each H2O molecule can efficiently form up to two H bonds with two H2O molecules. As a result, H2O molecules tend to aggregate into cyclic structures rather than chains on Al surfaces. Furthermore, the dissociation energy barrier of H2O drops with the increasing water coverage due to the presence of H bonds. Our results provide insight into interactions between water and Al, which can be extended to understand the interaction between water and other metal surfaces.

Gas-Dependent Active Sites on Cu/ZnO Clusters for CH3OH Synthesis.

This study describes an instantaneously gas-induced dynamic transition of an industrial Cu/ZnO/Al2O3 catalyst. Cu/ZnO clusters become "alive" and lead to a promotion in reaction rate by almost one magnitude, in response to the variation of the reactant components. The promotional changes are functions of either CO2-to-CO or H2O-to-H2 ratio which determines the oxygen chemical potential thus drives Cu/ZnO clusters to undergo reconstruction and allows the maximum formation of Cu-Zn2+ sites for CH3OH synthesis.

Applying early divergent characters in higher rank taxonomy of Melampsorineae (Basidiomycota, Pucciniales).

Rust fungi in the order Pucciniales represent one of the largest groups of phytopathogens, which occur on mosses, ferns to advanced monocots and dicots. Seven suborders and 18 families have been reported so far, however recent phylogenetic studies have revealed para- or polyphyly of several morphologically defined suborders and families, particularly in Melampsorineae. In this study, a comprehensive phylogenetic framework was constructed based on a molecular phylogeny inferred from rDNA sequences of 160 species belonging to 16 genera in Melampsorineae (i.e. Chrysomyxa, Cerospora, Coleopuccinia, Coleosporium, Cronartium, Hylospora, Melampsora, Melampsorella, Melampsoridium, Milesina, Naohidemyces, Pucciniastrum, Quasipucciniastrum, Rossmanomyces, Thekopsora, Uredinopsis). Our phylogenetic inference indicated that 13 genera are monophyletic with strong supports, while Pucciniastrum is apparently polyphyletic. A new genus, Nothopucciniastrum was therefore established and segregated from Pucciniastrum, with ten new combinations proposed. At the family level, this study further demonstrates the importance of applying morphologies of spore-producing structures (basidia, spermogonia, aecia, uredinia and telia) in higher rank taxonomy, while those traditionally applied spore morphologies (basidiospores, spermatia, aeciospores, urediniospores and teliospores) represent later diverged characters that are more suitable for the taxonomy at generic and species levels. Three new families, Hyalopsoraceae, Nothopucciniastraceae and Thekopsoraceae were proposed based on phylogenetic and morphological distinctions, towards a further revision of Pucciniales in line with the phylogenetic relationships.

Haplotype-phased and chromosome-level genome assembly of Puccinia polysora, a giga-scale fungal pathogen causing southern corn rust.

Rust fungi are characterized by large genomes with high repeat content and have two haploid nuclei in most life stages, which makes achieving high-quality genome assemblies challenging. Here, we described a pipeline using HiFi reads and Hi-C data to assemble a gigabase-sized fungal pathogen, Puccinia polysora f.sp. zeae, to haplotype-phased and chromosome-scale. The final assembled genome is 1.71 Gbp, with ~850 Mbp and 18 chromosomes in each haplotype, being currently one of the two giga-scale fungi assembled to chromosome level. Transcript-based annotation identified 47,512 genes for the dikaryotic genome with a similar number for each haplotype. A high level of interhaplotype variation was found with 10% haplotype-specific BUSCO genes, 5.8 SNPs/kbp, and structural variation accounting for 3% of the genome size. The P. polysora genome displayed over 85% repeat contents, with genome-size expansion and copy number increasing of species-specific orthogroups. Interestingly, these features did not affect overall synteny with other Puccinia species having smaller genomes. Fine-time-point transcriptomics revealed seven clusters of coexpressed secreted proteins that are conserved between two haplotypes. The fact that candidate effectors interspersed with all genes indicated the absence of a "two-speed genome" evolution in P. polysora. Genome resequencing of 79 additional isolates revealed a clonal population structure of P. polysora in China with low geographic differentiation. Nevertheless, a minor population differentiated from the major population by having mutations on secreted proteins including AvrRppC, indicating the ongoing virulence to evade recognition by RppC, a major resistance gene in Chinese corn cultivars. The high-quality assembly provides valuable genomic resources for future studies on disease management and the evolution of P. polysora.

Parasite-host network analysis provides insights into the evolution of two mistletoe lineages (Loranthaceae and Santalaceae).

Mistletoes are ecologically important parasitic plants, with > 1600 species from five lineages worldwide. Mistletoe lineages exhibit distinct patterns of species diversification and host specificity, however, the mechanisms underlying these differences are poorly understood. In this study, we analysed a comprehensive parasite-host network, including 280 host species from 60 families and 22 mistletoe species from two lineages (Santalaceae and Loranthaceae) in Xishuangbanna, located in a biodiversity hotspot of tropical Asia. We identified the factors that predict the infection strength of mistletoes. We also detected host specificity and the phylogenetic signal of mistletoes and their hosts. We found that this interaction network could be largely explained by a model based on the relative abundance of species. Host infection was positively correlated with diameter at breast height and tree coverage, but negatively correlated with wood density. Overall, closely related mistletoe species tend to interact more often with similar hosts. However, the two lineages showed a significantly different network pattern. Rates of host generality were higher in Loranthaceae than in Santalaceae, although neither lineage showed phylogenetic signal for host generality. This study demonstrates that the neutral interaction hypothesis provides suitable predictions of the mistletoe-host interaction network, and mistletoe species show significant phylogenetic signals for their hosts. Our findings also indicate that high species diversification in Loranthaceae may be explained by high rates of host generality and the evolutionary history shared by Loranthaceae species with diverse host plants in the tropics.

Site-Specific C-Terminal Fluorescent Labeling of Tau Protein.

Formation of Tau protein aggregates in neurons is a pathological hallmark of several neurodegenerative diseases, including Alzheimer's disease. Fluorescently labeled Tau protein is therefore useful to study the aggregation of these pathological proteins and to identify potential therapeutic targets. Conventionally, cysteine residues are used for labeling Tau proteins; however, the full-length Tau isoform contains two cysteine residues in the microtubule-binding region, which are implicated in Tau aggregation by forming intermolecular disulfide bonds. To prevent the fluorescent label from disturbing the microtubule binding region, we developed a strategy to fluorescently label Tau at its C-terminus while leaving cysteine residues unperturbed. We took advantage of a Sortase A-mediated transpeptidation approach to bind a short peptide (GGGH6-Alexa647) with a His-tag and a covalently attached Alexa 647 fluorophore to the C-terminus of Tau. This reaction relies on the presence of a Sortase recognition motif (LPXTG), which we attached to the C-terminus of recombinantly expressed Tau. We demonstrate that C-terminal modification of Tau protein results in no significant differences between the native and C-terminally labeled Tau monomer with regard to aggregation kinetics, secondary structure, and fibril morphology.

Genome-wide investigation and expression pattern of PHR family genes in cotton under low phosphorus stress.

Phosphorus starvation response (PHR) protein is an important transcription factor in phosphorus regulatory network, which plays a vital role in regulating the effective utilization of phosphorus. So far, the PHR genes have not been systematically investigated in cotton. In the present study, we have identified 22, 23, 41 and 42 PHR genes in G. arboreum, G. raimondii, G. hirsutum and G. barbadense, respectively. Phylogenetic analysis showed that cotton PHR genes were classified into five distinct subfamilies. The gene structure, protein motifs and gene expression were further investigated. The PHR genes of G. hirsutum from the same subfamily had similar gene structures, all containing Myb_DNA-binding and Myb_CC_LHEQLE conserved domain. The structures of paralogous genes were considerably conserved in exons number and introns length. The cis-element prediction in their promoters showed that genes were not only regulated by light induction, but also were related to auxin, MeJA, abscisic acid-responsive elements, of which might be regulated by miRNA. The expression analysis showed that the GhPHR genes were differentially expressed in different tissues under various stresses. Furthermore, GhPHR6, GhPHR11, GhPHR18 and GhPHR38 were significantly changed under low phosphorus stress. The results of this study provide a basis for further cloning and functional verification of genes related to regulatory network of low phosphorus tolerance in cotton.

A Review on Flexural Properties of Wood-Plastic Composites.

Wood-plastic composite (WPC) is a kind of composite material that is made of plastic and wood fiber or wood powder. Because it is mothproof, is resistant to corrosion, and has plasticity, among other advantages, it has been researched and used increasingly in building materials. The flexural property of WPC is an important subject in evaluating its mechanical properties. In this paper, wood-plastic raw materials and processing technology are introduced; the internal and external factors of WPC which affect the flexural properties are analyzed; the different ways of enhancing the bending capacity, including the surface pretreatment, addition of different modifiers (compatibility agent and coupling agent) etc. are summarized; and the methods of operation and strengthening effect are analyzed. This work provides a reference for further research in related fields.

A novel nomogram for predicting cancer-specific survival in women with uterine sarcoma: a large population-based study.

BACKGROUND: Uterine sarcoma (US) is a rare malignant uterine tumor with aggressive behavior and rapid progression. The purpose of this study was to constructa comprehensive nomogram to predict cancer-specific survival (CSS) of patients with US-based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective population-based study was conducted using data from patients with US between 2010 and 2015 from the SEER database. They were randomly divided into a training cohort and a validation cohort ata 7-to-3 ratio. Multivariate Cox analysis was performed to identify independent prognostic factors. Subsequently, a nomogram was established to predict patient CSS. The discrimination and calibration of the nomogram were evaluated by the concordance index (C-index) and the area under the curve (AUC). Finally, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the benefits of the new prediction model. RESULTS: A total of 3861 patients with US were included in our study. As revealed in multivariate Cox analysis, age at diagnosis, race, marital status, insurance record, tumor size, pathology grade, histological type, SEER stage, AJCC stage, surgery status, radiotherapy status, and chemotherapy status were found to be independent prognostic factors. In our nomogram, pathology grade had strongest correlation with CSS, followed by age at diagnosis and surgery status. Compared to the AJCC staging system, the new nomogram showed better predictive discrimination with a higher C-index in the training and validation cohorts (0.796 and 0.767 vs. 0.706 and 0.713, respectively). Furthermore, the AUC value, calibration plotting, NRI, IDI, and DCA also demonstrated better performance than the traditional system. CONCLUSION: Our study validated the first comprehensive nomogram for US, which could provide more accurate and individualized survival predictions for US patients in clinical practice.

Circ_0005576 Exerts an Oncogenic Role in Cervical Cancer via miR-1305-Dependent Regulation of PAIP1.

Cervical cancer (CC) is a leading cause of high morbidity and mortality in women worldwide. Circular RNAs (circRNAs) are considered to be essential regulators of various cancers, including CC. The purpose of this study was to investigate the role and mechanism of circ_0005576 in CC progression. The levels of circ_0005576, miR-1305, and poly(A)-binding protein-interacting protein 1 (PAIP1) were detected by quantitative real-time PCR (qRT-PCR) or western blot assay. The stability and location of circ_0005576 were determined by ribonuclease R (RNase R) assay and subcellular fractionation distribution assay, respectively. Cell proliferation was evaluated by CCK-8 assay, EDU incorporation assay, and colony formation assay. Cell migration and invasion were assessed by transwell assay. The interactions between miR-1305 and circ_0005576 or PAIP1 were validated by dual-luciferase reporter assay. The protein expression of cyclin D1, vimentin, and matrix metallopeptidase 9 (MMP9) was tested by western blot. Moreover, mice xenograft models were constructed to analyze tumor growth in vivo. Circ_0005576 and PAIP1 were upregulated, while miR-1305 was downregulated in CC tissues and cells. Circ_0005576 was a stable circRNA that was mainly distributed in the cytoplasm of cells. Knockdown of circ_0005576 suppressed the proliferation, migration, and invasion of CC cells, while the silence of miR-1305 facilitated the development of CC cells. Meanwhile, circ_0005576 could sponge miR-1305 to promote PAIP1 expression. Furthermore, PAIP1 overexpression relieved the influence of circ_0005576 silence on the growth of CC cells. Additionally, circ_0005576 silence hindered CC tumor growth in vivo. Circ_0005576 depletion suppressed tumor development in CC by regulating the miR-1305/PAIP1 axis, suggesting that circ_0005576 might be a potential biomarker for CC treatment.