Measurement of 19F(p, γ)20Ne reaction suggests CNO breakout in first stars.

Proposed mechanisms for the production of calcium in the first stars (population III stars)-primordial stars that formed out of the matter of the Big Bang-are at odds with observations1. Advanced nuclear burning and supernovae were thought to be the dominant source of the calcium production seen in all stars2. Here we suggest a qualitatively different path to calcium production through breakout from the 'warm' carbon-nitrogen-oxygen (CNO) cycle through a direct experimental measurement of the 19F(p, γ)20Ne breakout reaction down to a very low energy point of 186 kiloelectronvolts, reporting a key resonance at 225 kiloelectronvolts. In the domain of astrophysical interest2, at around 0.1 gigakelvin, this thermonuclear 19F(p, γ)20Ne rate is up to a factor of 7.4 larger than the previous recommended rate3. Our stellar models show a stronger breakout during stellar hydrogen burning than previously thought1,4,5, and may reveal the nature of calcium production in population III stars imprinted on the oldest known ultra-iron-poor star, SMSS0313-67086. Our experimental result was obtained in the China JinPing Underground Laboratory7, which offers an environment with an extremely low cosmic-ray-induced background8. Our rate showcases the effect that faint population III star supernovae can have on the nucleosynthesis observed in the oldest known stars and first galaxies, which are key mission targets of the James Webb Space Telescope9.

Rab25 is involved in hypospadias via the ß1 integrin/EGFR pathway.

BACKGROUND: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25-/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias. METHODS: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild-type (WT) and Rab25-/- mice. RESULTS: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25-/- mice. We demonstrated that Rab25 mediated hypospadias through the ß1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam. CONCLUSION: These findings suggest that Rab25 plays an essential role in hypospadias by activation of ß1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.

Cascade Dual Sites Modulate Local CO Coverage and Hydrogen-Binding Strength to Boost CO2 Electroreduction to Ethylene.

Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.

Efficacy and Safety of High-Dose Vitamin D Supplementation vs Solifenacin or Standard Urotherapy for Overactive Bladder Dry in Children: A Randomized Clinical Trial.

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.

HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

High-power 970†nm semiconductor disk laser: erratum.

An erratum is presented to modify a calculating error in our published manuscript ["High-power 970 nm semiconductor disk laser" Opt. Express31, 43963 (2023)10.1364/OE.506462 [CrossRef]]. All results throughout the manuscript and its conclusions are unaffected by this correction and remain valid.

Yb-doped mode-locked fiber laser with a hybrid structure of NPR and a Lyot filter as the saturable absorber.

Passively mode-locked fiber lasers based on a nonlinear polarization rotation (NPR) have attracted much attention due to their ability to generate short pulses with wide spectra and high peak power. However, environmental perturbations can easily cause the lasers to lose the mode-locked state and make it a challenge for practical application. The aim of this research is to improve the laser stability by inserting a Lyot filter into the mode-locked laser cavity. The experimental results indicate that the mode-locked state can be maintained when the radius of the fiber loop is changed from 7.5 to 1.5 cm, while the signal-to-noise ratio of the fundamental frequency remains almost the same. The tunability of the output power can be achieved by adding a half-wave plate (HWP) in the laser cavity without changing the pump power, while the mode-locked state remains stable. By adjusting the angle of the HWP2, the output power can be adjusted from 3.36 to 66.5 mW at repetition rate of 29.7 MHz.

Risk factors and timing of complication presentation following primary hypospadias repair in adolescents.

OBJECTIVES: To evaluate the risk factors for postoperative complications in adolescents who undergo primary hypospadias repair and determine the time required for complication detection. METHODS: Our study included patients classified as Tanner stages three to five who underwent primary hypospadias repairs at our hospital from January 2015 to August 2022. The patients' baseline information, clinical characteristics, postoperative complications, and time to complication detection were collected. Cox regression analysis, ROC curves, Kaplan-Meier survival analyses, and the Mann-Whitney U test were used. RESULTS: The study comprised 143 patients, with a median age of 12.58 years. Postoperative complications were experienced by 66 patients. The length of the urethral defect was identified as an independent risk factor for postoperative complications. The ROC curve analysis identified 3 cm as the optimal cutoff value for the length of the urethral defect. The median time to complication detection was 30.5 days (IQR 23 to 209.25). 89.4% of the complications were identified within the first year. Patients with a urethral defect of <3 cm experienced a significantly longer time for the detection of urethral fistula compared to those with a urethral defect of ≥3 cm (p = 0.047). CONCLUSIONS: Our data indicate that adolescents with a urethral defect ≥3 cm have a higher risk of postoperative complications. Although most complications were identified within the first year, conducting long-term follow-ups for adolescents is recommended to identify potential subsequent complications that may arise from persistent urethral alterations.

A near-complete genome assembly of Brassica rapa provides new insights into the evolution of centromeres.

Brassica rapa comprises many important cultivated vegetables and oil crops. However, Chiifu v3.0, the current B. rapa reference genome, still contains hundreds of gaps. Here, we presented a near-complete genome assembly of B. rapa Chiifu v4.0, which was 424.59 Mb with only two gaps, using Oxford Nanopore Technology (ONT) ultralong-read sequencing and Hi-C technologies. The new assembly contains 12 contigs, with a contig N50 of 38.26 Mb. Eight of the ten chromosomes were entirely reconstructed in a single contig from telomere to telomere. We found that the centromeres were mainly invaded by ALE and CRM long terminal repeats (LTRs). Moreover, there is a high divergence of centromere length and sequence among B. rapa genomes. We further found that centromeres are enriched for Copia invaded at 0.14 MYA on average, while pericentromeres are enriched for Gypsy LTRs invaded at 0.51 MYA on average. These results indicated the different invasion mechanisms of LTRs between the two structures. In addition, a novel repetitive sequence PCR630 was identified in the pericentromeres of B. rapa. Overall, the near-complete genome assembly, B. rapa Chiifu v4.0, offers valuable tools for genomic and genetic studies of Brassica species and provides new insights into the evolution of centromeres.

Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis.

BACKGROUND: Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain. METHODS: We constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD. RESULTS: We used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD. CONCLUSION: mtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.

Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages.

BACKGROUND: Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. METHODS: The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. RESULTS: OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. CONCLUSIONS: Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment.

Weakly Supervised Framework for Cancer Region Detection of Hepatocellular Carcinoma in Whole-Slide Pathologic Images Based on Multiscale Attention Convolutional Neural Network.

Visual inspection of hepatocellular carcinoma cancer regions by experienced pathologists in whole-slide images (WSIs) is a challenging, labor-intensive, and time-consuming task because of the large scale and high resolution of WSIs. Therefore, a weakly supervised framework based on a multiscale attention convolutional neural network (MSAN-CNN) was introduced into this process. Herein, patch-based images with image-level normal/tumor annotation (rather than images with pixel-level annotation) were fed into a classification neural network. To further improve the performances of cancer region detection, multiscale attention was introduced into the classification neural network. A total of 100 cases were obtained from The Cancer Genome Atlas and divided into 70 training and 30 testing data sets that were fed into the MSAN-CNN framework. The experimental results showed that this framework significantly outperforms the single-scale detection method according to the area under the curve and accuracy, sensitivity, and specificity metrics. When compared with the diagnoses made by three pathologists, MSAN-CNN performed better than a junior- and an intermediate-level pathologist, and slightly worse than a senior pathologist. Furthermore, MSAN-CNN provided a very fast detection time compared with the pathologists. Therefore, a weakly supervised framework based on MSAN-CNN has great potential to assist pathologists in the fast and accurate detection of cancer regions of hepatocellular carcinoma on WSIs.

High-power 970†nm semiconductor disk laser.

Semiconductor disk lasers (SDLs) have emerged at the frontier of laser technologies. Here, the chip design, packaging process, resonator, pumping strategy, etc. are optimized for the performance improvement of a 970 nm SDL. After optimization, a power of 70.3 W is attained under continuous wave (CW) operation, and the corresponding thermal resistance is around 0.49 K/W. The laser is highly efficient with a maximum slope efficiency of 58.2% and the pump threshold is only around 1.83 kW/cm2. Furthermore, the emission performances under quasi-continuous wave (QCW) pumping are also explored. Setting the duty cycle to about 11%, the chips can output a peak power of 138 W without thermal rollover, and the single pulse energy can reach about 13.6 mJ. As far as we know, they are the best results in terms of power/energy in this wavelength SDL. These explorations may help to understand the thermal characteristics in high-power SDLs and may also be regarded as an extension and enrichment of the earlier works on this topic.

Systematic analysis of RNASET2 gene as a potential prognostic and immunological biomarker in clear cell renal cell carcinoma.

BACKGROUND: RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) is still not well understood. METHODS: The RNASET2 expression matrix was extracted from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analyzed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancer in vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Moreover, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients. In vitro experiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodeling of the immune microenvironment in renal cell carcinoma. Furthermore, bioinformatics analysis and immunohistochemical staining showed that RNASET2 was positively correlated with the infiltration abundance of regulatory T cells. Finally, we mapped the mutational landscape of RNASET2 in ccRCC and found its predictive value for drug sensitivity. CONCLUSIONS: Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.

A complex locus regulates highly lobed-leaf formation in Brassica juncea.

KEY MESSAGE: Lineage-specific evolution of RCO was described in Brassicaceae. BjRCO.1 and BjRCO.2 within the complex locus regulated highly lobed-leaf formation in Brassica juncea. RCO regulates the formation of lobed leaves in Brassicaceae species. RCO originated from the duplication of LMI1-type sequences and evolved through gene duplication and loss within the Brassicaceae. However, the evolutionary process and diversification of RCO in different lineages of Brassicaceae remain unclear. Although the RCO locus in B. juncea has been associated with lobed-leaf formation, its complexity has remained largely unknown. This study involved the identification of 55 LMI1-like genes in 16 species of Brassicaceae through syntenic analysis. We classified these LMI1-like genes into two types, namely LMI1-type and RCO-type, based on their phylogenetic relationship. Additionally, we proposed two independent lineage-specific evolution routes for RCO following the divergence of Aethionema. Our findings revealed that the LMI1-like loci responsible for lobed-leaf formation in Brassica species are located on the LF subgenomes. For B. juncea (T84-66V2), we discovered that the complex locus underwent duplication through segments of nucleic acid sequence containing Exostosin-LMI1-RCO (E-R-L), resulting in the tandem presence of two RCO-type and two LMI1-type genes on chromosome A10. As additional evidence, we successfully mapped the complex locus responsible for highly lobed-leaf formation to chromosome A10 using a B. juncea F2 population, which corroborated the results of our evolutionary analysis. Furthermore, through transcriptome analysis, we clarified that BjRCO.1 and BjRCO.2 within the complex locus are functional genes involved in the regulation of highly lobed-leaf formation. The findings of this study offer valuable insights into the regulation of leaf morphology for the breeding of Brassica crops.

Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs.

The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.

A propensity score matching analysis of gasless endoscopic transaxillary thyroidectomy with five-settlement technique versus conventional open thyroidectomy in patients with papillary thyroid microcarcinoma.

BACKGROUND: In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. METHODS: The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. RESULT: After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto's thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). CONCLUSION: Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.

Bioinformatic analysis highlights SNHG6 as a putative prognostic biomarker for kidney renal papillary cell carcinoma.

PURPOSE: Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous malignancy and current systemic therapeutic strategies are difficult to achieve a satisfactory outcome for advanced disease. Meanwhile, there is a lack of effective biomarkers to predict the prognosis of KIRP. METHODS: Using TCGA, GTEx, UALCAN, TIMER, TIMER 2.0 and STRING databases, we analyzed the relationship of SNHG6 with KIRP subtypes, tumor-infiltrating immune cells and potential target mRNAs. Based on TCGA data, ROC curves, Kaplan-Meier survival analysis and COX regression analysis were performed to evaluate the diagnostic and prognostic value of SNHG6 in KIRP. Nomogram was used to predict 3- and 5-year disease-specific survival in KIRP patients. In addition, with the help of Genetic ontology and Gene set enrichment analysis, the biological processes and signalling pathways that SNHG6 may be involved in KIRP were initially explored. RESULTS: In patients with KIRP, SNHG6 was significantly upregulated and associated with a more aggressive subtype (lymph node involvement, pathological stage IV, CIMP phenotype) and poor prognosis. The ROC curve showed good diagnostic efficacy (AUC value: 0.828) and the C-index of the Nomogram for predicting DSS at 3 and 5 years was 0.920 (0.898-0.941). In the immune microenvironment of KIRP, SNHG6 expression levels were negatively correlated with macrophage abundance and positively correlated with cancer-associated fibroblasts. Furthermore, SNHG6 may promote KIRP progression by regulating the expression of molecules such as AURKB, NDC80, UBE2C, NUF2, PTTG1, CENPH, SPC25, CDCA3, CENPM, BIRC5, TROAP, EZH2. Last, GSEA suggests that SNHG6 may be involved in the regulation of the PPAR signalling pathway and the SLIT/ROBO signalling pathway. CONCLUSIONS: Our analysis suggests that a high SNHG6 expression status in KIRP is associated with a poorer prognosis for patients, and also elucidates some potential mechanisms contributing to this poorer outcome. This may provide new insights into the treatment and management of KIRP in the foreseeable future.

Age affects the diagnostic accuracy of the cancer ratio for malignant pleural effusion.

BACKGROUND AND OBJECTIVE: Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. METHODS: The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. RESULTS: Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52-0.68) and 0.63 (95% CI: 0.54-0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. CONCLUSION: Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. KEY MESSAGE: Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.