Greenhouse Gas Emissions during Oil Shale Crushing and Its Main Controlling Factors: A Contrast Study of Oil Shale in Yaojie and Fushun Areas, China.

Geological bodies are important sources of greenhouse gas (GHG) emissions. Organic-rich oil shale in sedimentary basins is a good gas source rock, the GHG in which will be released into the atmosphere during crushing to affect climate change. Quantitative calculations of GHG emissions during oil shale crushing were carried out on oil shales from the Yaojie (YJ) and Fushun (FS) mining areas in China. Organic geochemistry, X-ray diffraction, and pore structure analysis experiments, as well as the relationship between storage time and GHG emissions, were analyzed to investigate the main controlling factors of GHG release in different types of oil shales. The results showed that the CH4 and CO2 released from the YJ oil shale were 0.002-0.145 mL/g and 0.011-0.054 mL/g, respectively; the CH4 and CO2 released from the FS oil shale were 0.0001-0.0008 mL/g and 0.002-0.045 mL/g, respectively. Residual CH4 release was closely related to total organic carbon (TOC) and maturity: the CH4 released from the organic-rich and mature YJ oil shale was much higher than that of the FS oil shale, which is relatively organic-lean and immature. The control factors of the released CO2 vary in different regions: CO2 released from the YJ oil shale was somewhat affected by the TOC, while that released from the FS oil shale was mainly controlled by carbonate minerals and their contributing pores. The results of pore structure and organic maceral analyses indicated that both organic and inorganic pores of the YJ oil shale are occupied by asphaltenes, forming a key gas preservation mechanism of residual CH4 and CO2 as solutes dissolved in asphaltenes. In addition, CO2 has a greater absorptive capacity than CH4 and is therefore more difficult to release during the same crushing time. As oil shale is stored for longer periods, residual CH4 will be preferentially released to the atmosphere, while residual CO2 will be released in large quantities during crushing.

Optogenetic Stimulation of the Cardiac Vagus Nerve to Promote Heart Regenerative Repair after Myocardial Infarction.

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Pyrite Characteristics in Lacustrine Shale and Implications for Organic Matter Enrichment and Shale Oil: A Case Study from the Triassic Yanchang Formation in the Ordos Basin, NW China.

Pyrite is widely distributed in lacustrine shales and has become a research focus in unconventional oil and gas exploration. Pyrite morphology is useful for identifying different types of organic matter and assessing shale oil enrichment in organic-rich shale. Abundant pyrite is developed in the source rocks from the Chang 7 Member of the Yanchang Formation in the Ordos Basin, NW China. However, the relationship between different pyrite types and the differential enrichment of shale oil still needs to be clarified. The organic geochemistry, petrology, and isotopic composition of the Chang 7 Member samples were analyzed. The significance of pyrite types and sulfur isotopic compositions as indicators of depositional environments and shale oil enrichment was emphasized. The Chang 7 shales contain three pyrite morphologies, framboidal pyrite (type A), spherulitic pyrite (type B), and euhedral and anhedral pyrite (type C), and their aggregates. The sulfur isotopic compositions of pyrite (δ34Spy) in Chang 7 shales with different pyrite types exhibited regular patterns. The δ34S values of types A, B, and C pyrites were sequentially positive overall (average values are -2.739, 2.201, and 7.487‰ in sequence), indicating that type A pyrite was formed during the syn-sedimentary to early diagenetic stage and types B and C pyrites were formed during the early to middle diagenetic stage. Types A, B, and C pyrites showed sequentially increasing kerogen type index values and kerogen carbon isotope values (mean values of -31.59, -28.70, and -26.45‰, successively), indicating that the horizons where types A, B, and C pyrites developed correspond to types I, II, and III organic matter, respectively. Strong correlations between the pyrite content and oil components reveal that pyrite indicates shale oil enrichment. Moreover, variations in pyrite type significantly influenced the enrichment behavior of shale oil. Types A and B pyrites contributing to reservoir space showed shale oil enrichment. They promoted saturated hydrocarbon enrichment at >15% pyrite content, whereas type C pyrite did not indicate shale oil enrichment. These findings provide new insights into the differential enrichment of organic matter and shale oil and valuable guidance for the large-scale exploration and development of shale oil resources.

Association between lactate dehydrogenase to albumin ratio and acute kidney injury in patients with sepsis: a retrospective cohort study.

BACKGROUND: Serum lactate dehydrogenase to albumin ratio (LAR) is associated with poor outcomes in malignancy and pneumonia. However, there are few studies suggesting that LAR is associated with the occurrence of acute kidney injury (AKI) in patients with sepsis, which was investigated in this study. METHODS: We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary outcome was the occurrence of AKI within 2 days and 7 days. Multivariable logistic regression models were used to calculate odds ratios to validate the association between LAR and AKI, in-hospital mortality, RRT use, and recovery of renal function, respectively. RESULTS: A total of 4010 participants were included in this study. The median age of the participants was 63.5 years and the median LAR was 10.5. After adjusting for confounding variables, patients in the highest LAR quartile had a higher risk of AKI than those in the lowest LAR quartile within 2 days and 7 days, with odds ratios of 1.37 (95% confidence interval [CI]: 1.23-1.52) and 1.95 (95% CI: 1.72-2.22), respectively. The adjusted odds of AKI within 2 and 7 days were 1.16 (95% CI: 1.12-1.20) and 1.29 (95% CI: 1.24-1.35) for each 1 unit increase in LAR(log2), respectively. CONCLUSION: This study demonstrated that elevated LAR was associated with poor prognosis in patients with sepsis. The risk of AKI and in-hospital mortality increased, the need for RRT increased, and the chance of recovery of renal function decreased with the increase of LAR.

Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells.

BACKGROUND: Mitochondrial Ts translation elongation factor (TSFM) is an enzyme that catalyzes exchange of guanine nucleotides. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation. We have previously reported that TUFM regulates translation of beta-site APP cleaving enzyme 1 (BACE1) via ROS (reactive oxygen species)-dependent mechanism, suggesting a potential role in amyloid precursor protein (APP) processing associated with Alzheimer's disease (AD), which led to the speculation that TSFM may regulate APP processing in a similar way to TUFM. METHODS AND RESULTS: Here, we report that in cultured cells, knockdown or overexpression TSFM did not change protein levels in BACE1 and APP. Besides, the levels of cytoplasmic ROS and mitochondrial superoxide, in addition to ATP level, cell viability and mitochondrial membrane potential were not significantly altered by TSFM knockdown in the short term. Further transcriptome analysis revealed that expression of majority of mitochondrial genes were not remarkably changed by TSFM silencing. The possibility of TSFM involved in cardiomyopathy and cancer development was uncovered using bioinformatics analysis. CONCLUSIONS: Collectively, short-term regulation of TSFM level in cultured cells does not cause a significant change in proteins involved in APP processing, levels in ROS and ATP associated with mitochondrial function. Whereas our study could contribute to comprehend certain clinical features of TSFM mutations, the roles of TSFM in cardiomyopathy and cancer development might deserve further investigation.

Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation.

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Transformation and migration of Hg in a polluted alkaline paddy soil during flooding and drainage processes.

Mercury (Hg) contamination in paddy soils poses a health risk to rice consumers and the environmental behavior of Hg determines its toxicity. Thus, the variations of Hg speciation are worthy of exploring. In this study, microcosm and pot experiments were conducted to elucidate Hg transformation, methylation, bioaccumulation, and risk coupled with biogeochemical cycling of key elements in a Hg-polluted alkaline paddy soil. In microcosm and pot experiments, organic- and sulfide-bound and residual Hg accounted for more than 98% of total Hg, and total contents of dissolved, exchangeable, specifically adsorbed, and fulvic acid-bound Hg were less than 2% of total Hg, indicating a low mobility and environmental risk of Hg. The decrease of pH aroused from Fe(III), SO42-, and NO3- reduction promoted Hg mobility, whereas the increase of pH caused by Fe(II), S2-, and NH4+ oxidation reduced available Hg contents. Moreover, Fe-bearing minerals reduction and organic matter consumption promoted Hg mobility, whereas the produced HgS and Fe(II) oxidation increased Hg stability. During flooding, a fraction of inorganic Hg (IHg) could be transported into methylmercury (MeHg), and during drainage, MeHg would be converted back into IHg. After planting rice in an alkaline paddy soil, available Hg was below 0.3 mg kg-1. During rice growth, a portion of available Hg transport from paddy soil to rice, promoting Hg accumulation in rice grains. After rice ripening, IHg levels in rice tissues followed the trend: root > leaf > stem > grain, and IHg content in rice grain exceed 0.02 mg kg-1, but MeHg content in rice grain meets daily intake limit (37.45 µg kg-1). These results provide a basis for assessing the environmental risks and developing remediation strategies for Hg-contaminated redox-changing paddy fields as well as guaranteeing the safe production of rice grains.

METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-d-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment.

Cerebral furin deficiency causes hydrocephalus in mice.

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway. We have previously reported that cerebral overexpression of furin promotes cognitive functions in mice. Here, by generating the brain-specific furin conditional knockout (cKO) mice, we investigated the role of furin in brain development. We found that furin deficiency caused early death and growth retardation. Magnetic resonance imaging showed severe hydrocephalus. In the brain of furin cKO mice, impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expression of RAB28, a ciliary vesicle protein. In line with the widespread neuronal loss, ependymal cell layers were damaged. Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice; and astrocyte overgrowth was accompanied by the reduced expression of SOX9, indicating a disrupted differentiation into ependymal cells. Together, whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis, dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin cKO mice. The structural and molecular alterations provided a clue for further studying the potential mechanisms of furin.

Cotargeting CDK4/6 and BRD4 Promotes Senescence and Ferroptosis Sensitivity in Cancer.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including KRAS-mutant non-small cell lung cancer (NSCLC). However, the clinical efficacy of CDK4/6 inhibitors is limited due to frequent drug resistance and their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred resistance to the CDK4/6 inhibitor palbociclib in KRAS-mutant NSCLC cells. Inhibition of BRD4, either by RNA interference or small-molecule inhibitors, synergized with palbociclib to induce senescence in NSCLC cells and tumors, and the combination prolonged survival in a KRAS-mutant NSCLC mouse model. Mechanistically, BRD4-inhibition enhanced cell-cycle arrest and reactive oxygen species (ROS) accumulation, both of which are necessary for senescence induction; this in turn elevated GPX4, a peroxidase that suppresses ROS-triggered ferroptosis. Consequently, GPX4 inhibitor treatment selectively induced ferroptotic cell death in the senescent cancer cells, resulting in tumor regression. Cotargeting CDK4/6 and BRD4 also promoted senescence and ferroptosis vulnerability in pancreatic and breast cancer cells. Together, these findings reveal therapeutic vulnerabilities and effective combinations to enhance the clinical utility of CDK4/6 inhibitors. SIGNIFICANCE: The combination of cytostatic CDK4/6 and BRD4 inhibitors induces senescent cancer cells that are primed for activation of ferroptotic cell death by targeting GPX4, providing an effective strategy for treating cancer.

SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons.

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

Impact of Flooding-Drainage Alternation on Fe Uptake and Transport in Rice: Novel Insights from Iron Isotopes.

Iron (Fe) isotopes were utilized to provide insights into the temporal changes underlying Fe uptake and translocation during rice growth (tillering, jointing, flowering, and maturity stages) in soil-rice systems under typical flooding-drainage alternation. Fe isotopic composition (δ56Fe values) of the soil solution generally decreased at vegetative stages in flooding regimes but increased during grain-filling. Fe plaques were the prevalent source of Fe uptake, as indicated by the concurrent increase in the δ56Fe values of Fe plaques and rice plants during rice growth. The increasing fractionation magnitude from stem/nodes I to flag leaves can be attributed to the preferred phloem transport of light isotopes toward grains, particularly during grain-filling. This study demonstrates that rice plants take up heavy Fe isotopes from Fe plaque and soil solution via strategy II during flooding and the subsequent drainage period, respectively, thereby providing valuable insights into improving the nutritional quality during rice production.

METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner.

Acute lung injury (ALI) as well as its more severe form, acute respiratory distress syndrome (ARDS), frequently leads to an uncontrolled inflammatory response. N6-methyladenosine (m6A) modification was associated with the progression of several inflammatory diseases. However, the role of methyltransferase-like 14 (METTL14)-mediated m6A methylation in ALI/ARDS remains unclear. Here, we reported an increase in overall expression levels of m6A and METTL14 in circulating monocyte-derived macrophages recruited to the lung following ALI, which is correlated with the severity of lung injury. We further demonstrated the critical function of METTL14 in activating NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in vitro and in mouse models of ALI/ARDS, and validated NLRP3 as the downstream target of METTL14 by the m6A RNA immunoprecipitation (MeRIP) and RIP assays. Mechanistically, METTL14-methylated NLRP3 transcripts were subsequently recognized by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6A reader, which stabilized NLRP3 mRNA. Furthermore, we observed that IGF2BP2 knockdown diminished LPS-induced ALI in mice by downregulating NLRP3 expression. In summation, our study revealed that the molecular mechanism underlying the pathogenesis of ALI/ARDS involves METTL14-mediated activation of NLRP3 inflammasome in an IGF2BP2 dependent manner, thereby demonstrating the potential of METTL14 and IGF2BP2 as promising biomarkers and therapeutic targets for ALI/ARDS treatment.

PDDGCN: A Parasitic Disease-Drug Association Predictor Based on Multi-view Fusion Graph Convolutional Network.

The precise identification of associations between diseases and drugs is paramount for comprehending the etiology and mechanisms underlying parasitic diseases. Computational approaches are highly effective in discovering and predicting disease-drug associations. However, the majority of these approaches primarily rely on link-based methodologies within distinct biomedical bipartite networks. In this study, we reorganized a fundamental dataset of parasitic disease-drug associations using the latest databases, and proposed a prediction model called PDDGCN, based on a multi-view graph convolutional network. To begin with, we fused similarity networks with binary networks to establish multi-view heterogeneous networks. We utilized neighborhood information aggregation layers to refine node embeddings within each view of the multi-view heterogeneous networks, leveraging inter- and intra-domain message passing to aggregate information from neighboring nodes. Subsequently, we integrated multiple embeddings from each view and fed them into the ultimate discriminator. The experimental results demonstrate that PDDGCN outperforms five state-of-the-art methods and four compared machine learning algorithms. Additionally, case studies have substantiated the effectiveness of PDDGCN in identifying associations between parasitic diseases and drugs. In summary, the PDDGCN model has the potential to facilitate the discovery of potential treatments for parasitic diseases and advance our comprehension of the etiology in this field. The source code is available at https://github.com/AhauBioinformatics/PDDGCN .

APDDD: Animal parasitic diseases and drugs database.

Animal parasitic diseases not only have an economic impact, but also have serious social and public health impacts. Although antiparasitic drugs can treat these diseases, it seems difficult for users to comprehensively utilize the information, due to incomplete and difficult data collection. Thus, there is an urgent need to establish a comprehensive database, that includes parasitic diseases and related drugs. In this paper, we develop a knowledge database dedicated to collecting and analyzing animal parasitic diseases and related drugs, named Animal Parasitic Diseases and Drugs Database (APDDD). The current version of APDDD includes animal parasitic disease data of 8 major parasite classifications that cause common parasitic diseases and 96 subclass samples mined from many literature and authoritative books, as well as 182 antiparasitic drugs. Furthermore, we utilized APDDD data to add a knowledge graph representing the relationships between parasitic diseases, drugs, and the targeted gene of drugs acting on parasites. We hope that APDDD will become a good database for animal parasitic diseases and antiparasitic drugs research and that users can gain a more intuitive understanding of the relationships between parasitic diseases, drugs, and targeted genes through the knowledge graph.

Effects of zero-valent iron added in the flooding or drainage process on cadmium immobilization in an acid paddy soil.

Zero-valent iron (ZVI) is a promising material for the remediation of Cd-contaminated paddy soils. However, the effects of ZVI added during flooding or drainage processes on cadmium (Cd) retention remain unclear. Herein, Cd-contaminated paddy soil was incubated for 40 days of flooding and then for 15 days of drainage, and the underlying mechanisms of Cd immobilization coupled with Fe/S/N redox processes were investigated. The addition of ZVI to the flooding process was more conducive to Cd immobilization. Less potential available Cd was detected by adding ZVI before flooding, which may be due to the increase in paddy soil pH and newly formed secondary Fe minerals. Moreover, the reductive dissolution of Fe minerals promoted the release of soil colloids, thereby increasing significantly the surface sites and causing Cd immobilization. Additionally, the addition of ZVI before flooding played a vital role in Cd retention after soil drainage. In contrast, the addition of ZVI in the drainage phase was not conducive to Cd retention, which might be due to the rapid decrease in soil pH that inhibited Cd adsorption and further immobilization on soil surfaces. The findings of this study demonstrated that Cd availability in paddy soil was largely reduced by adding ZVI during the flooding period and provide a novel insight into the mechanisms of ZVI remediation in Cd-contaminated paddy soils.

The clinical association between coagulation indexes, platelet-related parameters, and bone metastasis of newly diagnosed prostate cancer.

BACKGROUND: At present, much evidence shows that many cancers have a high risk of thrombosis. Several studies have shown the prognostic value of platelet-related parameters and coagulation indexes in prostate cancer (PCa). However, the association between platelet-related parameters, coagulation indexes and bone metastasis of Pca is unclear. METHODS: A total of 234 pathologically diagnosed patients with Pca were consecutively collected and stratified into the bone metastasis group and non-bone metastasis group according to the results of the bone scan. ROC curve analysis was used to explore the auxiliary predictive value of single and combined parameters for bone metastasis in Pca patients. Univariate and multivariate Logistic regression analyses were used to determine the relationship between platelet-related parameters, coagulation indexes, and bone metastasis of Pca. RESULTS: Platelet count (PLT), fibrinogen (Fib), prostate-specific antigen (PSA), and D-dimer (DD) levels of the bone metastasis group were significantly higher than the non-bone metastasis group (P = 0.010, P < 0.001, P < 0.001, and P < 0.001, respectively). This study confirmed that PLT, PSA, DD and Fib have auxiliary predictive value for prostate cancer bone metastasis. After the combination of PLT, PSA, DD and Fib, the area under the curve, sensitivity and specificity increased significantly. The univariate logistic analysis demonstrated that PLT (OR: 1.008, P = 0.011), DD (OR: 2.690, P < 0.001), PSA (OR: 1.073, P < 0.001), Gleason score (OR: 7.060, P < 0.001), and Fib (OR: 2.082, P < 0.001) were significantly positively correlated with bone metastasis of Pca. Multivariate analysis showed that PSA (OR: 1.075, P < 0.001), DD (OR: 2.152, P < 0.001), Gleason score (OR: 2.904, P < 0.001), and Fib (OR: 1.706, P < 0.001) were independent risk factors for bone metastasis of Pca after adjusting for Age, BMI and other confounding factors. CONCLUSIONS: Higher platelet, D-dimer, prostate-specific antigen, Gleason score, and fibrinogen levels may predict a worse prognosis in patients with Pca. PLT, DD, and Fib, as readily available and relatively inexpensive indicators, help predict bone metastasis of Pca. It is suggested that PLT, DD and Fib may be helpful in the risk stratification of Pca.

Comprehensive multi-omics analysis of tryptophan metabolism-related gene expression signature to predict prognosis in gastric cancer.

Introduction: The 5-year survival of gastric cancer (GC) patients with advanced stage remains poor. Some evidence has indicated that tryptophan metabolism may induce cancer progression through immunosuppressive responses and promote the malignancy of cancer cells. The role of tryptophan and its metabolism should be explored for an in-depth understanding of molecular mechanisms during GC development. Material and methods: We utilized the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen tryptophan metabolism-associated genes via single sample gene set enrichment analysis (ssGSEA) and correlation analysis. Consensus clustering analysis was employed to construct different molecular subtypes. Most common differentially expressed genes (DEGs) were determined from the molecular subtypes. Univariate cox analysis as well as lasso were performed to establish a tryptophan metabolism-associated gene signature. Gene Set Enrichment Analysis (GSEA) was utilized to evaluate signaling pathways. ESTIMATE, ssGSEA, and TIDE were used for the evaluation of the gastric tumor microenvironment. Results: Two tryptophan metabolism-associated gene molecular subtypes were constructed. Compared to the C2 subtype, the C1 subtype showed better prognosis with increased CD4 positive memory T cells as well as activated dendritic cells (DCs) infiltration and suppressed M2-phenotype macrophages inside the tumor microenvironment. The immune checkpoint was downregulated in the C1 subtype. A total of eight key genes, EFNA3, GPX3, RGS2, CXCR4, SGCE, ADH4, CST2, and GPC3, were screened for the establishment of a prognostic risk model. Conclusion: This study concluded that the tryptophan metabolism-associated genes can be applied in GC prognostic prediction. The risk model established in the current study was highly accurate in GC survival prediction.