Automated segmentation and volume prediction in pediatric Wilms' tumor CT using nnu-net.

BACKGROUND: Radiologic volumetric evaluation of Wilms' tumor (WT) is an important indicator to guide treatment decisions. However, due to the heterogeneity of the tumors, radiologists have main-guard differences in diagnosis that can lead to misdiagnosis and poor treatment. The aim of this study was to explore whether CT-based outlining of WT foci can be automated using deep learning. METHODS: We included CT intravenous phase images of 105 patients with WT and double-blind outlining of lesions by two radiologists. Then, we trained an automatic segmentation model using nnUnet. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used to assess the performance. Next, we optimized the automatic segmentation results based on the ratio of the three-dimensional diameter of the lesion to improve the performance of volumetric assessment. RESULTS: The DSC and HD95 was 0.83 ± 0.22 and 10.50 ± 8.98 mm. The absolute difference and percentage difference in tumor size was 72.27 ± 134.84 cm3 and 21.08% ± 30.46%. After optimization according to our method, it decreased to 40.22 ± 96.06 cm3 and 10.16% ± 9.70%. CONCLUSION: We introduce a novel method that enhances the accuracy of predicting WT volume by integrating AI automated outlining and 3D tumor diameters. This approach surpasses the accuracy of using AI outcomes alone and has the potential to enhance the clinical evaluation of pediatric patients with WT. By intertwining AI outcomes with clinical data, this method becomes more interpretive and offers promising applications beyond Wilms tumor, extending to other pediatric diseases.

A Cohort Study on the Correlation Between Serum Uric Acid Trajectory and New-Onset Hypertension Based on Longitudinal Health Examination Data in Henan Area.

Objective: To explore the correlation between serum uric acid (SUA) trajectories and new-onset hypertension, to provide scientific basis for the prevention and treatment of hypertension. Methods: The study cohort was composed of 4372 subjects who met the inclusion criteria in the cohort study of Henan physical examination population. According to the SUA values of the subjects' physical examination from 2017 to 2019, three different SUA trajectory groups were determined by R LCTM tools, namely low stability group, medium stability group and high stability group. The incidence of hypertension during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product limit method, and the correlation between different SUA trajectories and new-onset hypertension was analyzed by Cox proportional hazards regression model. Results: The incidence rate of hypertension increased with the increase of SUA locus, which was 4.65%, 9.18% and 12.43% respectively, and the difference was statistically significant (P<0.001). After adjusting multiple confounding factors, such as gender, waist circumference (WC), blood pressure, body mass index (BMI), fasting plasma glucose (FPG) and blood lipid by Cox proportional hazards regression model, the risk of hypertension in SUA medium stability and high stability group was still 1.476 times (95% CI: 1.089~2.000) and 1.692 times (95% CI: 1.152~2.484) of low-stable SUA group (P<0.05). Conclusion: The risk of hypertension increases with the increase of SUA level in the long-term normal range. It is necessary to carry out the intervention for hypertension with long-term normal high value to avoid the progress of hypertension disease, to achieve the purpose of early prevention of hypertension.

Development of a nomogram to predict the prognosis of patients with secondary bone tumors in the intensive care unit: a retrospective analysis based on the MIMIC IV database.

PURPOSE: The present study aimed to develop a nomogram to predict the prognosis of patients with secondary bone tumors in the intensive care unit to facilitate risk stratification and treatment planning. METHODS: We used the MIMIC IV 2.0 (the Medical Information Mart for Intensive Care IV) to retrieve patients with secondary bone tumors as a study cohort. To evaluate the predictive ability of each characteristic on patient mortality, stepwise Cox regression was used to screen variables, and the selected variables were included in the final Cox proportional hazard model. Finally, the performance of the model was tested using the decision curve, calibration curve, and receiver operating characteristic (ROC) curve. RESULTS: A total of 1028 patients were enrolled after excluding cases with missing information. In the training cohort, albumin, APSIII (Acute Physiology Score III), chemotherapy, lactate, chloride, hepatic metastases, respiratory failure, SAPSII (Simplified Acute Physiology Score II), and total protein were identified as independent risk factors for patient death and then incorporated into the final model. The model showed good and robust prediction performance. CONCLUSION: We developed a nomogram prognostic model for patients with secondary bone tumors in the intensive care unit, which provides effective survival prediction information.

A free-standing lithium phosphorus oxynitride thin film electrolyte promotes uniformly dense lithium metal deposition with no external pressure.

Lithium phosphorus oxynitride (LiPON) is an amorphous solid electrolyte that has been extensively studied over the last three decades. Despite the promise of pairing it with various electrode materials, LiPON's rigidity and air sensitivity set limitations to understanding its intrinsic properties. Here we report a methodology to synthesize LiPON in a free-standing form that manifests remarkable flexibility and a Young's modulus of ∼33 GPa. We use solid-state nuclear magnetic resonance and differential scanning calorimetry to quantitatively reveal the chemistry of the Li/LiPON interface and the presence of a well-defined LiPON glass-transition temperature of 207 °C. Combining interfacial stress and a gold seeding layer, our free-standing LiPON shows a uniformly dense deposition of lithium metal without the aid of external pressure. This free-standing LiPON film offers opportunities to study fundamental properties of LiPON for interface engineering for solid-state batteries.

Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

Deep quantum neural networks on a superconducting processor.

Deep learning and quantum computing have achieved dramatic progresses in recent years. The interplay between these two fast-growing fields gives rise to a new research frontier of quantum machine learning. In this work, we report an experimental demonstration of training deep quantum neural networks via the backpropagation algorithm with a six-qubit programmable superconducting processor. We experimentally perform the forward process of the backpropagation algorithm and classically simulate the backward process. In particular, we show that three-layer deep quantum neural networks can be trained efficiently to learn two-qubit quantum channels with a mean fidelity up to 96.0% and the ground state energy of molecular hydrogen with an accuracy up to 93.3% compared to the theoretical value. In addition, six-layer deep quantum neural networks can be trained in a similar fashion to achieve a mean fidelity up to 94.8% for learning single-qubit quantum channels. Our experimental results indicate that the number of coherent qubits required to maintain does not scale with the depth of the deep quantum neural network, thus providing a valuable guide for quantum machine learning applications with both near-term and future quantum devices.

Effects of Clostridium butyricum on Growth Performance, Intestinal Health, and Disease Resistance of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) Fed with Cottonseed Protein Concentrate (CPC) Replacement of Fishmeal.

An 8-week feeding trial was conducted to investigate the effects of C. butyricum on the growth performance, microbiota, immunity response, and disease resistance in hybrid grouper fed with cottonseed protein concentrate (CPC) replacement of fishmeal. Six groups of isonitrogenous and isolipid diets were formulated including a positive control group (50% fishmeal, PC), a negative control group (CPC replaced 50% of fishmeal protein, NC), and Clostridium butyricum supplemented with 0.05% (C1, 5 × 108 CFU/kg), 0.2% (C2, 2 × 109 CFU/kg), 0.8% (C3, 8 × 109 CFU/kg), and 3.2% (C4, 3.2 × 1010 CFU/kg), respectively, to the NC group. The results showed that weight gain rate and specific growth rate were significantly higher in the C4 group than that in the NC group (P < 0.05). After supplementation with C. butyricum, the amylase, lipase, and trypsin activities were significantly higher than the NC group (P < 0.05; except group C1), and the same results were obtained for intestinal morphometry. The intestinal proinflammatory factors were significantly downregulated, and the anti-inflammatory factors were significantly upregulated in the C3 and C4 groups compared with the NC group after supplementation with 0.8%-3.2% C. butyricum (P < 0.05). At the phylum level, the PC, NC, and C4 groups were dominated by the Firmicutes and the Proteobacteria. At the genus level, the relative abundance of Bacillus in the NC group was lower than that in the PC and C4 groups. After supplementation with C. butyricum, grouper in the C4 group showed significantly higher resistance to V. harveyi than the NC group (P < 0.05). Above all, taking into account the effects of immunity and disease resistance, it was recommended to supplement 3.2% C. butyricum in the diet of grouper fed the replacement of 50% fishmeal protein by CPC.

The isolation, identification, whole-genome sequencing of Clostridium butyricum LV1 and its effects on growth performance, immune response, and disease-resistance of Litopenaeus vannamei.

In this study, a strain of Clostridium butyricum was isolated from the intestine of Litopenaeus vannamei with the method of anaerobic microbial isolation and culture. Next, the probiotic properties of LV1 were evaluated with susceptibility tests, tolerance tests, and whole genome sequencing in vivo and in vitro, followed by the analysis of the effect of LV1 on the growth performance, immune response, and disease resistance of Litopenaeus vannamei. According to the results, the 16 S rDNA sequence of LV1 was 100% homolofgous to the reference sequence of Clostridium butyricum. Moreover, LV1 was resistant to several antibiotics including amikacin, streptomycin, and gentamicin and highly tolerated artificial gastric and artificial intestinal fluids. The whole genome of LV1 was 4625,068 bp in size and included 4336 coding genes. Among these genes, GO, KEGG, and COG databases exhibited the highest number of genes annotated to metabolic pathway classes and 105 genes annotated as glycoside hydrolases. Meanwhile, 176 virulence genes were predicted. The use of diets supplemented with 1.2 × 109 CFU/kg of LV1 live cells significantly increased the weight gain and specific growth rates of Litopenaeus vannamei and the activity of serum superoxide dismutase, glutathione peroxidase, acid phosphatase, and alkaline phosphatase (P < 0.05). Meanwhile, the use of these diets markedly improved the relative expression of intestinal immunity- and growth-related genes. In conclusion, LV1 has excellent probiotic properties. Specifically, the addition of 1.2 × 109 CFU/kg of LV1 live cells to the diet improved the growth performance, immune response, and disease-resistance of Litopenaeus vannamei.

Structural Transformation in a Sulfurized Polymer Cathode to Enable Long-Life Rechargeable Lithium-Sulfur Batteries.

Sulfurized polyacrylonitrile (SPAN) represents a class of sulfur-bonded polymers, which have shown thousands of stable cycles as a cathode in lithium-sulfur batteries. However, the exact molecular structure and its electrochemical reaction mechanism remain unclear. Most significantly, SPAN shows an over 25% 1st cycle irreversible capacity loss before exhibiting perfect reversibility for subsequent cycles. Here, with a SPAN thin-film platform and an array of analytical tools, we show that the SPAN capacity loss is associated with intramolecular dehydrogenation along with the loss of sulfur. This results in an increase in the aromaticity of the structure, which is corroborated by a >100× increase in electronic conductivity. We also discovered that the conductive carbon additive in the cathode is instrumental in driving the reaction to completion. Based on the proposed mechanism, we have developed a synthesis procedure to eliminate more than 50% of the irreversible capacity loss. Our insights into the reaction mechanism provide a blueprint for the design of high-performance sulfurized polymer cathode materials.

Differential diagnosis of prostate cancer and benign prostatic hyperplasia based on DCE-MRI using bi-directional CLSTM deep learning and radiomics.

Dynamic contrast-enhanced MRI (DCE-MRI) is routinely included in the prostate MRI protocol for a long time; its role has been questioned. It provides rich spatial and temporal information. However, the contained information cannot be fully extracted in radiologists' visual evaluation. More sophisticated computer algorithms are needed to extract the higher-order information. The purpose of this study was to apply a new deep learning algorithm, the bi-directional convolutional long short-term memory (CLSTM) network, and the radiomics analysis for differential diagnosis of PCa and benign prostatic hyperplasia (BPH). To systematically investigate the optimal amount of peritumoral tissue for improving diagnosis, a total of 9 ROIs were delineated by using 3 different methods. The results showed that bi-directional CLSTM with ± 20% region growing peritumoral ROI achieved the mean AUC of 0.89, better than the mean AUC of 0.84 by using the tumor alone without any peritumoral tissue (p = 0.25, not significant). For all 9 ROIs, deep learning had higher AUC than radiomics, but only reaching the significant difference for ± 20% region growing peritumoral ROI (0.89 vs. 0.79, p = 0.04). In conclusion, the kinetic information extracted from DCE-MRI using bi-directional CLSTM may provide helpful supplementary information for diagnosis of PCa.

Identification and validation of crucial lnc-TRIM28-14 and hub genes promoting gastric cancer peritoneal metastasis.

BACKGROUND: Gastric cancer peritoneal metastasis (GCPM) is an important cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) play a key role in the regulation of GCPM, but the underlying mechanisms have not been elucidated. METHODS: High-throughput RNA sequencing (RNA-seq) was performed on four groups of clinical specimens (non-metastatic gastric cancer primary tumor, adjacent normal gastric mucosal tissue, gastric cancer primary tumor with peritoneal metastasis and adjacent normal gastric mucosal tissue). After sequencing, many lncRNAs and mRNAs were screened for further Weighted Gene Co-expression Network Analysis (WGCNA). GCPM-related hub lncRNAs and genes were identified by cytoHubba and validated by Quantitative real-time PCR (qRT-PCR), Receiver operating characteristic curve (ROC) analysis and Kaplan-Meier survival analysis. GO, KEGG and GSEA showed GCPM-related pathways. Correlation analysis revealed the potential relationship between hub lncRNAs and genes. RESULTS: By analyzing lncRNA expression data by WGCNA, we found that blue module was highly correlated with GCPM (r = 0.44, p = 0.04) and six lncRNAs involved in this module (DNM3OS, lnc-MFAP2-53, lnc-PPIAL4C-4, lnc-RFNG-1, lnc-TRIM28-14 and lnc-YARS2-4) were identified. We then performed qRT-PCR validation of gastric cancer specimens and found that the expression of lnc-RFNG-1 and lnc-TRIM28-14 was significantly increased in gastric cancer tissues with peritoneal metastasis. Kaplan-Meier survival analysis showed shorter overall survival time (OS) for gastric cancer patients with high expression of lnc-TRIM28-14. Receiver operating characteristic curve (ROC) analysis showed that lnc-TRIM28-14 could improve the sensitivity and specificity of GCPM diagnosis. In addition, we identified three key mRNAs (CD93, COL3A1 and COL4A1) associated with gastric cancer peritoneal metastasis through WGCNA analysis and clinical specimen validation. Moreover, there was a positive correlation between lnc-TRIM28-14 and the expression of CD93 and COL4A1 in gastric cancer peritoneal metastasis, suggesting a regulatory relationship between them. Subsequent GO, KEGG and GSEA analysis suggested that ECM-receptor interaction and focal adhesion were the hub pathways of GCPM. CONCLUSION: In summary, lnc-RFNG-1, lnc-TRIM28-14, CD93, COL3A1 and COL4A1 could be novel tumor biomarkers and potential therapeutic targets for GCPM.

Ultralow-Temperature Li/CFx Batteries Enabled by Fast-Transport and Anion-Pairing Liquefied Gas Electrolytes.

Lithium fluorinated-carbon (Li/CFx ) is one of the most promising chemistries for high-energy-density primary energy-storage systems in applications where rechargeability is not required. Though Li/CFx demonstrates high energy density (>2100 Wh kg-1 ) under ambient conditions, achieving such a high energy density when exposed to subzero temperatures remains a challenge, particularly under high current density. Here, a liquefied gas electrolyte with an anion-pair solvation structure based on dimethyl ether with a low melting point (-141 °C) and low viscosity (0.12 mPa s, 20 °C), leading to high ionic conductivity (>3.5 mS cm-1 ) between -70 and 60 °C is reported. Besides that, through systematic X-ray photoelectron spectroscopy integrated with transmission electron microscopy characterizations, the interface of CFx is evaluated for low-temperature performance. The fast transport and anion-pairing solvation structure of the electrolyte are concluded to bring about reduced charge-transfer resistance at low temperatures, which results in significantly enhanced performance of Li/CFx cells (1690 Wh kg-1 , -60 °C based on active materials). Utilizing 50 mg cm-2 loading electrodes, the Li/CFx still displays 1530 Wh kg-1 at -60 °C. This work provides insights into the electrolyte design that may overcome the operational limits of batteries in extreme environments.

CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1.

Metastasis is an important factor contributing to poor prognosis in patients with gastric cancer; yet, the molecular mechanism leading to this cell behavior is still not well understood. In this study, we explored the role of cysteine protease inhibitor SN (Cystatin SN, CST1) in promoting gastric cancer metastasis. We hypothesized that CST1 could regulate gastric cancer progression by regulating GPX4 and ferroptosis. Whole transcriptome sequencing suggested that the expression of CST1 was significantly increased in metastatic cancer, and high CST1 expression was correlated with a worse prognosis. Our data further confirmed that the overexpression of CST1 may significantly promote the migration and invasion of gastric cancer cells in vitro and enhance liver, lung, and peritoneal metastasis of gastric cancer in nude mice. Meanwhile, high expression of CST1 promoted the epithelial-mesenchymal transition (EMT) of gastric cancer cells. Mechanistically, a co-immunoprecipitation experiment combined with mass spectrometry analysis confirmed that CST1 could interact with GPX4, a key protein regulating ferroptosis. CST1 relieves GPX4 ubiquitination modification by recruiting OTUB1, improving GPX4 protein stability and reducing intracellular reactive oxygen species (ROS), thereby inhibiting ferroptosis and, in turn, promoting gastric cancer metastasis. Moreover, clinical data suggested that CST1 is significantly increased in peripheral blood and ascites of gastric cancer patients with metastasis; multivariate Cox regression model analysis showed that CST1 was an independent risk factor for the prognosis of gastric cancer patients. Overall, our results elucidated a critical pathway through which high CST1 expression protects gastric cancer cells from undergoing ferroptosis, thus promoting its progression and metastasis. CST1 may be used as a new oncological marker and potential therapeutic target for gastric cancer metastasis.

ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis.

The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.

Current Challenges in Efficient Lithium-Ion Batteries' Recycling: A Perspective.

Li-ion battery (LIB) recycling has become an urgent need with rapid prospering of the electric vehicle (EV) industry, which has caused a shortage of material resources and led to an increasing amount of retired batteries. However, the global LIB recycling effort is hampered by various factors such as insufficient logistics, regulation, and technology readiness. Here, the challenges associated with LIB recycling and their possible solutions are summarized. Different aspects such as recycling/upcycling techniques, worldwide government policies, and the economic and environmental impacts are discussed, along with some practical suggestions to overcome these challenges for a promising circular economy for LIB materials. Some potential strategies are proposed to convert such challenges into opportunities to maintain the global expansion of the EV and other LIB-dependent industries.

Pulmonary effects of exposure to indium and its compounds: cross-sectional survey of exposed workers and experimental findings in rodents.

BACKGROUND: Many studies have shown that occupational exposure to indium and its compounds could induce lung disease. Although animal toxicological studies and human epidemiological studies suggest indium exposure may cause lung injury, inflammation, pulmonary fibrosis, emphysema, pulmonary alveolar proteinosis, and even lung cancer, related data collected from humans is currently limited and confined to single workplaces, and the early effects of exposure on the lungs are not well understood. OBJECTIVES: This study combined population studies and animal experiments to examine the links of indium with pulmonary injury, as well as its mechanism of action. A cross-sectional epidemiological study of indium-exposed workers from China was conducted to evaluate associations between occupational indium exposure and serum biomarkers of early effect. This study also compares and analyzes the causal perspectives of changes in human serum biomarkers induced by indium compound exposure and indium exposure-related rat lung pathobiology, and discusses possible avenues for their recognition and prevention. METHODS: This is a study of 57 exposed (at least 6 h per day for one year) workers from an indium ingot production plant, and 63 controls. Indium concentration in serum, urine, and airborne as exposure indices were measured by inductively coupled plasma-mass spectrometry. Sixteen serum biomarkers of pulmonary injury, inflammation, and oxidative stress were measured using ELISA. The associations between serum indium and 16 serum biomarkers were analyzed to explore the mechanism of action of indium on pulmonary injury in indium-exposed workers. Animal experiments were conducted to measure inflammatory factors levels in bronchoalveolar lavage fluid (BALF) and lung tissue protein expressions in rats. Four different forms of indium compound-exposed rat models were established (intratracheal instillation twice per week, 8 week exposure, 8 week recovery). Model I: 0, 1.2, 3, and 6 mg/kg bw indium tin oxide group; Model II: 0, 1.2, 3, and 6 mg/kg bw indium oxide (In2O3) group; Model III: 0, 0.523, 1.046, and 2.614 mg/kg bw indium sulfate (In2(SO4)3) group; Model IV: 0, 0.065, 0.65, and 1.3 mg/kg bw indium trichloride (InCl3) group. Lung pathological changes were assessed by hematoxylin & eosin, periodic acid Schiff, and Masson's staining, transmission electron microscopy, and the protein changes were determined by immunohistochemistry. RESULTS: In the production workshop, the airborne indium concentration was 78.4 µg/m3. The levels of serum indium and urine indium in indium-exposed workers were 39.3 µg/L and 11.0 ng/g creatinine. Increased lung damage markers, oxidative stress markers, and inflammation markers were found in indium-exposed workers. Serum indium levels were statistically and positively associated with the serum levels of SP-A, IL-1ß, IL-6 in indium-exposed workers. Among them, SP-A showed a duration-response pattern. The results of animal experiments showed that, with an increase in dosage, indium exposure significantly increased the levels of serum indium and lung indium, as well as the BALF levels of IL­1ß, IL­6, IL­10, and TNF­α and up-regulated the protein expression of SP-A, SP-D, KL-6, GM-CSF, NF-κB p65, and HO-1 in all rat models groups. TEM revealed that In2(SO4)3 and InCl3 are soluble and that no particles were found in lung tissue, in contrast to the non-soluble compounds (ITO and In2O3). No PAS-staining positive substance was found in the lung tissue of In2(SO4)3 and InCl3 exposure groups, whereas ITO and In2O3 rat models supported findings of pulmonary alveolar proteinosis and interstitial fibrosis seen in human indium lung disease. ITO and InCl3 can accelerate interstitial fibrosis. Findings from our in vivo studies demonstrated that intra-alveolar accumulation of surfactant (immunohistochemistry) and characteristic cholesterol clefts granulomas of indium lung disease (PAS staining) were triggered by a specific form of indium (ITO and In2O3). CONCLUSIONS: In indium-exposed workers, biomarker findings indicated lung damage, oxidative stress and an inflammatory response. In rat models of the four forms of indium encountered in a workplace, the biomarkers response to all compounds overall corresponded to that in humans. In addition, pulmonary alveolar proteinosis was found following exposure to indium tin oxide and indium oxide in the rat models, and interstitial fibrosis was found following exposure to indium tin oxide and indium trichloride, supporting previous report of human disease. Serum SP-A levels were positively associated with indium exposure and may be considered a potential biomarker of exposure and effect in exposed workers.

A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma.

Background: Glioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis. Methods: A necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features. Results: Three necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis. Conclusions: Our necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.

Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men.

It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of "harmful bacteria" such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of "beneficial bacteria" such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

Potential active compounds and molecular mechanism of Xuefu Zhuyu decoction for atherosclerosis, based on network pharmacology and molecular docking.

To explore the potential active compounds and molecular mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of atherosclerosis (AS) based on network pharmacology and molecular docking. The effective components and action targets of XFZYD were screened by using TCMSP database. And then, the action targets of AS were collected by GeneCards database. The intersection targets between the effective components' targets of XFZYD and AS-related action targets were used to construct PPI networks. GO and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these intersection targets. Finally, molecular docking software was used to excavate the active compounds of the core targets VEGFA and AKT1. We detected 225 active components of XFZYD, and found that quercetin, kaempferol, luteolin, naringenin, ß-sitosterol, isorhamnetin, stigmasterol, baicalein, nobiletin, and ß-carotene are the potential active compounds of XFZYD; STAT3, IL6, JUN, VEGFA, MAPK14, and AKT1 are the core target proteins of the active compounds, among which VEGFA and AKT1 are the key target proteins. PPI network results showed that ß-carotene, quercetin, kaempferol, luteolin, and naringenin had higher degree values and more corresponding targets than other 5 active compounds and had the stable binding ability to regulatory proteins VEGFA and AKT1. The core components ß-carotene, quercetin, kaempferol, and luteolin exerted their therapeutic effects on AS by acting on the key target proteins VEGFA and AKT1 to regulate fluid shear stress and the AGE-RAGE signaling pathway and IL-17 signaling pathway of diabetic complications of AS. The molecular docking results showed that VEGFA and AKT1 had great docking ability with the targeted active compounds, and ß-carotene is the best. The active components of XFZYD, including ß -carotene, quercetin, kamanol, and luteolin, can act on VEGFA and AKT1. These active ingredients play a role in alleviating and treating AS by regulating fluid shear stress and participating in signaling pathways such AS AGE-RAGE of atherosclerosis and diabetes mellitus complicated with AS. ß-carotene is a potential inhibitor of VEGFA and AKT1 and treats AS through antioxidant action.