Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Glycogen accumulation and phase separation drives liver tumor initiation.

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.

A New Strategy for the Design of Triple-Phase Eutectic High-Entropy Alloys Based on Infinite Solid Solution and Pseudo-Ternary Method.

Eutectic high-entropy alloys (EHEAs) have combined both high-entropy alloys and eutectic alloy contributions, with excellent castability and high-temperature application potential. Yet, multielement/triple-phase eutectic high-entropy alloy (TEHEA) designs remain puzzling. This work proposed a new strategy based on an infinite solid solution and pseudo-ternary model to reveal the puzzle of TEHEAs. The designed triple-phase eutectic high-entropy alloys (TEHEAs) with more than seven elements were identified as face-centered cubic (FCC), ordered body-centered cubic (B2), and Laves phase structures. In this work, the alloy C showcases outstanding comprehensive mechanical properties, offering a novel avenue for the design of high-performance EHEAs.

Grafted Alkene Chains: Triggers for Defeating Contact Thermal Resistance in Composite Elastomers.

The pursuit of enhancing the heat transfer performance of composite elastomers as the thermal interface materials (TIMs) is a compelling and timely endeavor, given the formidable challenges posed by interfacial thermal transport in the domains of energy science, electronic technology, etc. Despite the efficacy of phase change materials (PCMs) in enhancing composite elastomers' interfacial compatibility, thereby reducing contact thermal resistance for heat transfer improvement, their leakage post-transition has impeded the widespread adoption of this approach. Herein, a strategy is proposed for developing a solid-solid phase change composite elastomer by grafting alkene chains onto the crosslink network to eliminate the possibility of leakage. A series characterization suggest that the resulting material possesses a self-adjusting interfacial compatibility feature to help reduce contact thermal resistance for heat transfer facilitating. The investigations on adhesion strength and surface energy reveal that the presence of amorphous grafted alkane chains at the interface facilitates easier absorption onto the contacting solid surface, enhancing intermolecular interactions at the interface to promote across-boundary heat transfer. By integrating these findings with the thermal performance evaluation of composite elastomers using a real test vehicle, valuable insights are gained for the design of composite elastomers, establishing their suitability as TIMs in relevant fields.

SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs.

Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Secretome from myoblasts statically loaded at low intensity promotes tenocyte proliferation via the IGF-1 receptor pathway.

Exercise is widely recognized as beneficial for tendon healing. Recently, it has been described that muscle-derived molecules secreted in response to static exercise influence tendon healing. In this study, the optimal static loading intensity for tendon healing and the composition of secretome released by myoblasts in response to different intensities of static strain were investigated. In an in vitro coculture model, myoblasts were mechanically loaded using a Flexcell Tension System. Tenocytes were seeded on transwell inserts that allowed communication between the tenocytes and myoblasts without direct contact. Proliferation and migration assays, together with RNA sequencing, were used to determine potential cellular signaling pathways. The secretome from myoblasts exposed to 2% static loading increased the proliferation and migration of the cocultured tenocytes. RNA-seq analysis revealed that this loading condition upregulated the expression of numerous genes encoding secretory proteins, including insulin-like growth factor-1 (IGF-1). Confirmation of IGF-1 expression and secretion was carried out using qPCR and enzyme-linked immunosorbt assay (ELISA), revealing a statistically significant upregulation in response to 2% static loading in comparison to both control conditions and higher loading intensities of 5% and 10%. Addition of an inhibitor of the IGF-1 receptor (PQ401) to the tenocytes significantly reduced myoblast secretome-induced tenocyte proliferation. In conclusion, IGF-1 may be an important molecule in the statically loaded myoblast secretome, which is responsible for influencing tenocytes during exercise-induced healing.

Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk.

BACKGROUND: Lipid pathways play a crucial role in psoriatic arthritis development, and some lipid-lowering drugs are believed to have therapeutic benefits due to their anti-inflammatory properties. Traditional observational studies face issues with confounding factors, complicating the interpretation of causality. This study seeks to determine the genetic link between these medications and the risk of psoriatic arthritis. METHODS: This drug target study utilized the Mendelian randomization strategy. We harnessed high-quality data from population-level genome-wide association studies sourced from the UK Biobank and FinnGen databases. The inverse variance-weighted method, complemented by robust pleiotropy methods, was employed. We examined the causal relationships between three lipid-lowering agents and psoriatic arthritis to unveil the underlying mechanisms. RESULTS: A significant association was observed between genetically represented proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and a decreased risk of psoriatic arthritis (odds ratio [OR]: 0.51; 95% CI 0.14-0.88; P < 0.01). This association was further corroborated in an independent dataset (OR 0.60; 95% CI 0.25-0.94; P = 0.03). Sensitivity analyses affirmed the absence of statistical evidence for pleiotropic or genetic confounding biases. However, no substantial associations were identified for either 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or Niemann-Pick C1-like 1 inhibitors. CONCLUSIONS: This Mendelian randomization analysis underscores the pivotal role of PCSK9 in the etiology of psoriatic arthritis. Inhibition of PCSK9 is associated with reduced psoriatic arthritis risk, highlighting the potential therapeutic benefits of existing PCSK9 inhibitors.

Self-assembly of colloids with competing interactions confined in spheres.

At low temperatures, colloidal particles with short-range attractive and long-range repulsive interactions can form various periodic microphases in bulk. In this paper, we investigate the self-assembly behaviour of colloids with competing interactions under spherical confinement by conducting molecular dynamics simulations. We find that the cluster, mixture, cylindrical, perforated lamellar and lamellar structures can be obtained, but the details of the ordered structures are different from those in bulk systems. Interestingly, the system tends to form more perforated structures when confined in smaller spheres. The mechanism behind this phenomenon is driven by the relationship between the energy of the ordered structures and the bending of the confinement wall, which is different from the mechanism in copolymer systems.

Gaussian Process Regression for State-to-State Integral Cross Sections: The Case of the O + O2 Collision Dissociation Reactions.

Research on hypersonic vehicles has become increasingly important worldwide in recent years. However, accurately simulating the dynamics of the nonequilibrium high-temperature reactions that are in the hypersonic flow around the vehicles presents a significant challenge as a large number of states and transitions are accessible even for the smallest atom-diatom reaction systems. It is quite difficult, sometimes even impossible, to exhaustively investigate all relevant combinations or determine high-dimensional analytical representations for the state-to-state reaction probabilities. In this study, we used Gaussian process regression (GPR) to fit a model based on only 807 QCT data for training. The confidence interval of the GPR prediction and the Kullback-Leibler (KL) divergence were used to help minimize the sampling amount of data for fitting the converged GPR model. The model aims to predict the state-to-state integral cross section (ICS) of the O + O2 → 3O dissociation reaction under random initial conditions (Et, v, j). In total, it took almost a month to obtain this converged GPR model, but it took only a few seconds to predict the ICS value for any initial condition. For 330 initial conditions not included in the training set, the mean-square error (MSE) between the QCT-calculated ICSs and the GPR-predicted ones is only 0.08 Å2 and the R2 is 0.9986, indicating that the GPR model can replace the direct expensive QCT calculation with high accuracy. Finally, we calculated the equilibrium dissociation rate coefficients based on the StS ICS values predicted by the GPR model, and the results were in good agreement with available experimental and theoretical results. Thus, this study provides an effective and accurate approach to the extensive direct state-to-state reaction dynamic calculations.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

Portable electrochemical sensing platform based on amidated GO-MOF and PEDOT:PSS for high-efficient detection of ponceau 4R.

A promising electrochemical sensing platform for the detection of ponceau 4R in food has been fabricated based on the carboxylated graphene oxide (GO-COOH), metal-organic framework (MOF) UIO-66-NH2, and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). To this end GO-COOH was covalently coupled with UIO-66-NH2 through amide reaction, endowing the material (GO-CONH-UIO-66) unique hierarchical pores and high chemical stability and as a result improving the conductivity of MOF and the dispersion of GO. After the addition of PEDOT:PSS into GO-CONH-UIO-66, the continuity and conductivity of the composite (PEDOT:PSS/GO-CONH-UIO-66) have been further enhanced, due to the high conductivity, favorable film-forming, and hydrophilic properties of PEDOT:PSS. Systematic electrochemical experiments confirm that the PEDOT:PSS/GO-CONH-UIO-66/GCE shows satisfactory electrochemical sensing properties towards the detection of ponceau 4R, with a wide linear detection range of 0.01-30 µM, a low limit of detection of 3.33 nM, and a high sensitivity of 0.606 µA µM-1 cm-2. The PEDOT:PSS/GO-CONH-UIO-66 sensing platform was successfully used to detect ponceau 4R in beverage, and the detection results were compared with  high-performance liquid chromatography. As a result, the PEDOT:PSS/GO-CONH-UIO-66 composite shows a promising application prospect for rapid detection of ponceau 4R in food and will play significant role in food safety detection and supervision.

Effect of rapid rehabilitation care on surgical site wound infection and pain in patients with intertrochanteric femoral fractures: A meta-analysis.

This study examines the effects of rapid rehabilitation on surgical site wound infections and pain in patients with intertrochanteric femoral fractures. A computerised search was conducted for randomised controlled trials (RCTs) on rapid rehabilitation care in patients undergoing surgery for intertrochanteric femoral fractures published in the China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Database, VIP, PubMed, Embase, Cochrane Library and Web of Science. The search was conducted from the time of the database construction to August 2023. Two investigators independently performed literature screening, data extraction and quality assessment based on predefined inclusion and exclusion criteria. Meta-analysis was performed via RevMan 5.4 software. Encompassing 21 studies involving 2004 patients, with 1007 patients receiving rapid rehabilitation care and 997 receiving routine care, our analysis revealed that rapid rehabilitation care significantly reduced postoperative complications (odds ratio [OR] = 0.24, 95% confidence interval [CI]: 0.17-0.33, p < 0.001), wound infections (OR = 0.30, 95% CI: 0.14-0.65, p = 0.002) and hospital stay (mean difference [MD] = -5.23, 95% CI: -6.03 to -4.43, p < 0.001). Moreover, compared with routine care, it notably improved wound pain (MD = -1.51, 95% CI: -1.98 to -1.05, p < 0.001) in patients undergoing surgery for intertrochanteric femoral fractures. Our findings underscore the effectiveness of rapid rehabilitation care in reducing wound pain, postoperative complications and wound infections among patients with intertrochanteric femoral fractures.

Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling.

SMYD2 is a lysine histone methyl transferase involved in various cancers epigenetically via methylating histone H3K4, and H3K36. c-Myc is one of the major drivers of prostate cancer (PCa) initiation and progression. The roles of SMYD2 in PCa and the regulators of c-Myc activity in PCa are still under-researched. SMYD2 expression and survival outcomes in PCa cohorts were analyzed by bioinformatics analysis. SMYD2 protein levels were detected in PCa tissues by immunohistochemistry. SMYD2 knockdown cells were established to identify the effects of SMYD2 on cell growth in vitro and in vivo. GSEA and RNA sequencing were adopted to reconnoiter the signaling regulated by SMYD2 in PCa. The relationship between SMYD2 and c-Myc was examined by western blot analysis, qPCR, and immunohistochemistry. SMYD2 specific inhibitor-AZ505 was used to pharmacologically inhibit SMYD2 function in vitro and in vivo. SMYD2 expression increased in PCa tissues compared with benign prostate tissues and higher SMYD2 expression was associated with a higher risk of biochemical relapse after radical prostatectomy. SMYD2 knockdown inhibited the growth of PCa cells both in vitro and in vivo. Furthermore, high SMYD2 levels conduced to activated c-Myc signaling in PCa cells. Importantly, the pharmacological intervention of SMYD2 by AZ505 significantly repressed PCa cell growth both in vitro and in vivo. Our findings indicate that SMYD2 inhibition restrains PCa cell proliferation by regulating c-Myc signaling and provide evidence for the potential practice of SMYD2 targeting in the treatment of PCa.

A Carbazole-1,8-Disulfonamide-Derived Cryptand Receptor for Anion Recognition.

A novel cryptand-like anion receptor 1 was synthesized in reasonable yield by a one-step condensation reaction. The UV-vis spectroscopic titrations indicated that cryptand 1 bound AcO- in preference to other monovalent anions (including its competing F- and H2PO4-) in CH3CN, generating a 1:1 binding complex with Ka = 51,000 M-1. Moreover, the crystal structures revealed that the acetate ion was encapsulated inside the cryptand's cavity in a 1:1 manner, through multiple N-H···O hydrogen bonds (although having two different crystal forms).

Association of serum uric acid levels with bone mineral density and the presence of osteoporosis in Chinese patients with Parkinson's disease: a cross-sectional study.

INTRODUCTION: As the population ages, the incidence of osteoporosis among patients suffering from Parkinson's disease (PD) will surge continually, and the ensuing disability from falls is becoming a serious social burden. Due to its antioxidant properties, much literature has indicated the possible ability of serum uric acid (UA) to prevent ageing-related diseases caused by oxidative stress, including osteoporosis and PD. Therefore, this study was for exploring the connection of serum UA levels with bone mineral density (BMD) and the osteoporosis presence in Chinese PD patients. MATERIALS AND METHODS: A cross-sectional design was used to statistically analyze 42 clinical parameters obtained from 135 patients with PD treated in Wuhan Tongji Hospital during 2020-2022. Multiple stepwise linear regression and multiple logistic regression analyses were constructed for identifying the association of serum UA levels with BMD as well as osteoporosis in PD patients, respectively. With receiver operative characteristic (ROC) curves, the optimal cutoff value was acquired for serum UA in the diagnosis of osteoporosis. RESULTS: According to the regression analysis adjusted for confounders, serum UA levels in PD patients had positive correlation with BMD at each site and negative correlation with the presence of osteoporosis (P < 0.05 for all). ROC curves determined that the optimal cutoff value for UA to perform well in diagnosing osteoporosis in PD patients was 284.27 µmol/L (P < 0.001). CONCLUSION: Relatively higher serum UA levels in the physiological range can work as a biomarker of higher BMD, and were strongly linked to lower prevalence of osteoporosis in Chinese PD patients.

Possibility analysis of thyroid imaging parameters for dose adjustment in 131I treatment of hyperthyroidism.

BACKGROUND: To determine the thyroid uptake rate by correcting the background and analyze its clinical significance. METHODS: The study included 161 patients with hyperthyroidism. The thyroid uptake rate was calculated by drawing a 100 pixels ROI (region of interest) background, above and below the thyroid and correcting the thyroid ROI for background counting. At the same time, the clinical baseline characteristic parameters such as age and thyroid volume etc. of patients with hyperthyroidism were collected. The consistency of 99mTcO4uptake rate before treatment and 131I-uptake rate after treatment, and the correlation between uptake rate of thyroid and baseline characteristic parameters were also analyzed. RESULTS: The uptake rate of 99mTcO4 was found positively correlated with 3 h-radioactive iodine uptake (RAIU), 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity free triiodothyronine (FT3) and free thyroxine (FT4), and showed negative correlation with age, effective half-life (P<0.05). The uptake rate of 131I was found positively correlated with 3 h-RAIU, 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity, FT3, FT4 (P<0.05). In patients with positive thyrotrophin receptor antibody (TRAb), a significant positive correlation between uptake rate of 99mTcO4 and 131I (P<0.05) was observed. There was a high consistency between pretreatment uptake rate of 99mTcO4 and post-treatment uptake rate of 131I (P=0.009; W=0.7). CONCLUSIONS: The corrected thyroid uptake rate is remarkably correlated with clinical characteristic parameters of patients, which can be used to comprehensively evaluate the comprehensive condition of patients with hyperthyroidism.

Advances of circRNA-miRNA-mRNA regulatory network in cerebral ischemia/reperfusion injury.

Ischemic stroke (IS) is the most common type of stroke, and its pathophysiological process is more complex. In recent years, the key regulatory roles of non-coding RNA (miRNA, circRNA) and mRNA in the development of IS have attracted more attention. In the process of cerebral ischemia/reperfusion injury, circRNA can regulate nerves, blood vessels and immune system through miRNA/mRNA axis, so as to affect the neurovascular unit of IS. The combination of these noncoding RNAs and mRNAs can be used as non-invasive biomarkers and therapeutic tools for IS diagnosis, prognosis and brain injury. Therefore, it is very important to study the potential molecular mechanism, activation pathway and treatment methods of circRNA/miRNA/mRNA network in IS. This review will focus on the latest progress of circRNA/miRNA/mRNA regulatory network, we have also included some circRNAs, which does not mediate through a miRNA, so we also include circRNA -mRNA network. And explore the application prospect of these RNAs as potential therapeutic targets in the prevention and treatment of IS.

Transformation mechanism of methylphosphonate to methane by Burkholderia sp: Insight from multi-labeled water isotope probing and transcriptomic.

Methylphosphonate (MPn), has been identified as a likely source of methane in aerobic ocean and may be responsible for the "ocean methane paradox", that is oversaturation of dissolved methane in oxic sea waters. However, the mechanism underlying the cleavage of C-P bonds during microbial degradation is not well understood. Using multi-labeled water isotope probing (MLWIP) and transcriptome analysis, we investigated the phosphate oxygen isotope systematics and mechanisms of microbial-mediated degradation of MPn in this study. In the aerobic culture containing MPn as the only phosphorus source, there was a significant release of inorganic phosphate (149.4 µmol/L) and free methane (268.3 mg/L). The oxygen isotopic composition of inorganic phosphorus (δ18OP) of accumulated released phosphate was 4.50‰, 23.96‰, and 40.88‰, respectively, in the corresponding 18O-labeled waters of -10.3‰, 9.9‰, and 30.6‰, and the slope obtained in plots of δ18OP versus the oxygen isotopic composition of water (δ18OW) was 0.89. Consequently, 89% of the oxygen atoms (Os) in phosphate (PO4) were exchanged with 18O-labeled waters in the medium, while the rest were exchanged with intracellular metabolic water. It has been confirmed that the C-P bond cleavage of MPn occurs in the cell with both ambient and metabolic water participation. Moreover, phn gene clusters play significant roles to cleave the C-P bond of MPn for Burkholderia sp. HQL1813, in which phnJ, phnM and phnI genes are significantly up-regulated during MPn decomposition to methane. In conclusion, the aerobic biotransformation of MPn to free methane by Burkholderia sp. HQL1813 has been elucidated, providing new insights into the mechanism that bio-cleaves C-P bonds to produce methane aerobically in aqueous environments for representative phosphonates.

Competing risk nomogram for predicting prognosis of patients with spinal and pelvic chordoma: A SEER-based retrospective study.

PURPOSE: Recently, competing risk nomograms were widely applied to predict prognosis in numerous tumors other than chordoma. Here, we aimed to construct and validate a competing-risk-based prognostic nomogram to predict 3- and 5-year cancer-specific death (CSD) in patients with spinal and pelvic chordoma. METHODS: All chordoma patient data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) resource, and a total of 485 chordoma patients were eventually included in this study. Multivariate competing risk model and multivariate Cox model were used to determine independent prognostic factors, respectively, and the results of the two models were compared. Nomogram was employed to visualize the competing risk model. The discrimination, calibration, and clinical utility of this model were evaluated by Harrell concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Ten-fold cross-validation was further utilized to validate the prognostic nomogram. RESULTS: Significant prognostic factors affecting CSD were age (P = 0.016), localized involvement (P < 0.0001), and radical resection (P < 0.001) in the multivariate competing risk model. C-indexes were 0.799 and 0.76, and AUC were 0.812 and 0.778 for 3- and 5-year CSD. Calibration plots demonstrated the nomogram was well-fitted, and DCA indicated good clinical utility. The nomogram showed good performance in the 10-fold cross-validation. CONCLUSION: We successfully built the first competing-risk-based nomogram to predict clinical outcomes in patients with spinal and pelvic chordoma. This well-established nomogram hopes to help clinicians with precise prognostic assessment and thus improve clinical outcomes.