Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

Causal relationship between gut microbiota and gastric cancer: A two­sample Mendelian randomization analysis.

The gut microbiota is associated with GC; however, the causal association between the gut microbiota and GC remains to be determined. The aim of the present study was to investigate the causal association between gut microbiota and gastric cancer (GC) from the perspective of Mendelian randomization (MR). The present study performed MR analysis using summary statistics from a genome-wide association study of the gut microbiome and GC. Inverse-variance weighted, MR-Egger and weighted median methods were used to investigate the causal relationship between gut microbiota and GC. Heterogeneity tests were performed using Cochrane's Q statistic. Horizontal polytropy was detected using Mendelian Randomization Pleiotropy RESidual Sum and Outlier were eliminated. Estimates from MR indicated that nine gut microorganism remained stable with regard to acceptance of heterogeneity and sensitivity methods. Among them, the genera Prevotella 7, Roseburia and Ruminococcaceae UCG014 were associated with an increased risk of GC; by contrast, the family Enterobacteriaceae, the genera Allisonella, Lachnospiraceae FCS020, Ruminococcaceae UCG004 and Ruminococcaceae UCG009, and the order Enterobacteriales decreased the risk of GC development. The present study demonstrated the potential importance of modulating the abundance of gut microbiota for the prevention and treatment of GC.

Industrial fluoride emissions and their spatial characteristics in the Nansi Lake Basin, Eastern China.

Excessive fluoride emissions threaten ecological stability and human health. Previous studies have noted that industrial sources could be significant. However, quantifying industrial fluoride emissions has not been yet reported. In this study, both bottom-up and top-down approaches were used to estimate the fluoride emissions in the Nansi Lake Basin. Global and local spatial autocorrelation were adopted to reveal the spatial agglomeration effects. The fluoride emissions calculated by the bottom-up approach were larger than those calculated by the top-down method. The highest fluoride input mainly occurred in Zoucheng and Mudan. The highest fluoride emissions mainly occurred in Zoucheng and Rencheng using the bottom-up approach. The highest fluoride emissions mainly occurred in Zoucheng and Yanzhou using the top-down approach. Mining and washing of bituminous coal and anthracite (BAW) was the most significant source of fluoride input and emissions. A significant spatial agglomeration effect of fluoride emissions was found. These findings could provide a method for accurate industrial fluoride emission estimation, complement the critical data on the fluoride emissions of main industrial sectors, and provide a scientific basis for tracing fluoride sources.

Cooperative interactions between Veillonella ratti and Lactobacillus acidophilus ameliorate DSS-induced ulcerative colitis in mice.

Veillonella and Lactobacillus species are key regulators of a healthy gut environment through metabolic cross-feeding, influencing lactic acid and short-chain fatty acid (SCFA) levels, which are crucial for gut health. This study aims to investigate how Veillonella ratti (V. ratti) and Lactobacillus acidophilus (LA) interact with each other and alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in a mouse model. We assess their metabolic interactions regarding carbon sources through co-culturing in a modified medium. In the in vitro experiments, V. ratti and LA were inoculated in mono-cultures and co-culture, and viable cell counts, OD600, pH, lactic acid, glucose and SCFAs were measured. For the in vivo experiment, 60 C57BL/6 mice were randomly divided into five groups and administered V. ratti and LA alone or in combination via oral gavage (1 × 109 CFU mL-1 per day per mouse) for 14 days. On the seventh day, 2.5% DSS was added to the drinking water to induce colitis. The effects of these probiotics on UC were evaluated by assessing intestinal barrier integrity and intestinal inflammation in the gut microenvironment. In vitro results demonstrated that co-culturing V. ratti with LA significantly increased viable cell numbers, lactic acid production, and SCFA production, while reducing pH and glucose levels in the medium. In vivo findings revealed that intervention with V. ratti, particularly in combination with LA, alleviated symptoms, including weight loss, colon shortening, and tissue damage. These probiotics mitigated intestinal inflammation by down-regulating pro-inflammatory molecules, such as IL-6, IL-1ß, IL-γ, iNOS, and IFN-γ, as well as oxidative stress markers, including MDA and MPO. Concurrently, they upregulated the activity of anti-inflammatory enzymes, namely, SOD and GSH, and promoted the production of SCFAs. The combined intervention of V. ratti and LA significantly increased acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in cecal contents. Furthermore, the intervention of V. ratti and LA increased the abundance of beneficial bacteria, such as Akkermansia, while reducing the abundance of harmful bacteria, such as Escherichia-Shigella and Desulfovibrio, thereby mitigating excessive inflammation. These findings highlight the enhanced therapeutic effects resulting from the interactions between V. ratti and LA, demonstrating the potential of this combined probiotic approach.

Versatile nicotinamide enabling dendrite-free and efficient deposition for aqueous Zn-I2 batteries.

This study introduces a versatile electrolyte additive, nicotinamide, for zinc anodes, aiming to facilitate uniform deposition and suppress water-induced side reactions. The molecular structure, consisting of a pyridine ring and an amide function group, endows NTA molecules with the ability to regulate electrolyte pH, enhance nucleation overpotential, and constrain 2D diffusion of Zn2+. As a result, the full battery configuration with this additive achieved an impressive lifespan of over 10 000 cycles.

The Genomic and Proteomic Profiles of NTRK Genes and Trk Receptors in Liver Hepatocellular Carcinoma.

Background: The neurotrophic tyrosine kinase (NTRK) gene family includes NTRK1, NTRK2, and NTRK3, which encode tropomyosin receptor kinases TrkA, TrkB, and TrkC, respectively. This study aimed to initially assess the genomic and proteomic profiles of NTRK genes and Trk receptors in liver hepatocellular carcinoma (LIHC). Methods: The ONCOMINE, UALCAN, GEPIA, cBioPortal, FusionGDB, SurvivalMeth, and the Human Protein Atlas databases were searched for NTRK gene expression and protein data in LIHC. Immunohistochemistry was used to detect pan-Trk expression across a commercial microarray containing 96 hepatocellular carcinoma (HCC) and 94 para-cancerous tissue spots. A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for pan-Trk. Student's t- and chi-square tests were the main statistical analyses used. Results: The transcriptional levels of NTRK genes in LIHC were not significantly different from healthy controls. Using UALCAN and GEPIA, only high expression of NTRK2 was significantly associated with longer disease-free survival (P = 0.004). The alteration frequencies were low (7% in NTRK1, 1.7% in NTRK2, and 2% in NTRK3). The methylation levels of NTRK genes were all significantly different as analyzed by UALCAN; the high-risk group displayed an unfavorable prognosis compared with the low-risk group for NTRK1 (P = 0.033) and NTRK3 (P = 0.005). The median H-score of pan-Trk in HCC and para-cancerous tissues was not statistically different (186.31 ± 23.86 and 192.38 ± 21.06, P = 0.065). No differences were observed in clinicopathological features of HCC with the median H-score for pan-Trk expression (p > 0.05). The survival rate of patients with pan-Trk expression was also not significantly different. Conclusion: The alteration frequency was low in NTRK genes, including gene fusion and methylation levels. Therefore, pan-Trk expression in HCC tissue has limited value in clinicopathological features and prognosis.

Expression and prognostic impact of NTF3 and TrkC in hepatocellular carcinoma.

BACKGROUND: Treatment of patients with NTRK fusion-positive cancers using first-generation tropomyosin-related kinase (Trk) inhibitors is associated with high response rates, regardless of tumor histology. However, there have been few studies on neurotrophin-3 (NTF3) and TrkC ligands in hepatocellular carcinoma (HCC). METHODS: We used immunohistochemistry to evaluate NTF3 and TrkC expression levels in tissue samples. Gene expression profiling interactive analysis was used to determine TrkC and NTF3 expression in HCC. Western blotting, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assays were utilized to analyze TrkC and NTF3 levels in HCC cell lines. Proliferation tests and cell migration were also explored. RESULTS: NTF3 and TrkC levels were lower in HCC tissue (median H- scores 149.09 and 54.60, respectively) than those in para-cancerous tissue (192.69 and 71.70, respectively); no statistical difference was found in the survival rate. Positive correlations were observed between NTF3 and TrkC levels in both HCC and para-cancerous tissues. Alpha-fetoprotein was the only clinical characteristic associated with TrkC levels. The transcription of NTF3 was lower in HCC samples compared to normal samples. NTF3 overexpression inhibited the proliferation of MHCC97-L and HepG2 cells but did not significantly affect cell migration. CONCLUSIONS: The transcription of NTF3 was lower in HCC samples compared to normal samples, indicating a potential association with disease-free survival and overall survival in HCC. NTF3 and TrkC expression levels were lower in HCC tissues than those in para-cancerous tissues. Our results indicate that NTF3 may be a prognostic factor for HCC.

Study on the effect of koumiss on reactivation of Toxoplasma gondii infection.

Toxoplasma gondii is an obligate intracellular parasite that infects nucleated cells of all warm-blooded animals, and most patients have latent infections. The latent infection will be reactivated in the immunocompromised or immunocompromised individuals, which will lead to severe toxoplasmosis. At present, less research has been focused on the reactivation of T. gondii infection. Koumiss is a kind of fermented milk made from fresh mare's milk through natural fermentation that can be applied to clinical and rehabilitation medicine to mitigate the development of various diseases due to its unique functional characteristics. In this study, we explored the antagonistic effect of koumiss on reactivation of T. gondii infection. Mice were treated with dexamethasone to establish a reactivation model after infection with T. gondii and then treated with koumiss. The survival rate, SHIRPA test, serum cytokine levels, organ parasite burden and intestinal microbiota were measured, respectively. Our results showed that koumiss treatment improved the clinical symptoms of mice, significantly reduced the organ parasite burden of mice, and improved the composition and structure of intestinal flora. This study provides new evidence for the alleviation and treatment of toxoplasmosis and provides a novel idea for the development and utilization of koumiss.

Antibiotic susceptibility and biofilm-forming ability of Veillonella strains.

INTRODUCTION: Veillonella, known as early colonizers in oral biofilms, take part in some infections in human. Biofilm refers to complex, sessile communities of microbes, which function as strong barriers for bacteria to survive. Biofilm matrixes surrounding bacteria enable them to withstand harsh conditions, protect against immune cells, etc., and also make them resistant to antimicrobial treatments. Thus, the knowledge of antibiotic susceptibility and biofilm formation of Veillonella will shed light on their resistance mechanism. MATERIALS AND METHOD: Their morphology was observed by scanning electron microscopy (SEM). According to the performance standards for antibiotic susceptibility testing of the Clinical & Laboratory Standards Institute, the Agar dilution method was used to study the susceptibility of Veillonella strains to eight antibiotics (ampicillin, piperacillin-tazobactam, cefoxitin, tetracycline, moxifloxacin, clindamycin, metronidazole, and vancomycin). In addition, we applied the crystal violet staining method to reveal the processes of biofilm formation of these Veillonella strains. RESULTS: V. rogosae, V. nakazawae, and V. parvula were isolated from oral cavities of healthy adults and V. ratti was isolated from dairy goat droppings. Observations by scanning electron microscopy showed that Veillonella were spherical and arranged in single or short chains. The diameter of a single cell was about 0.3-0.5 µm. The Minimum Inhibitory Concentrations (MICs) of the antibiotics were determined and the results showed that these four strains were all sensitive to cefoxitin, tetracycline, moxifloxacin, clindamycin and metronidazole. Among the four strains, V. ratti was resistant to piperacillin-tazobactam, and V. rogosae and V. nakazawae were resistant to ampicillin. The vancomycin susceptibility of the four Veillonella strains varied greatly. The MICs of vancomycin against V. rogosae and V. ratti were greater than 256 µg/mL but the MICs of vancomycin against V. nakazawae and V. parvula were less than 2 µg/mL. V. parvula had significantly higher biofilm-forming ability than the other three strains (p < 0.05) and V. nakazawae had the weakest biofilm-forming ability. CONCLUSION: In this study, V. rogosae, V. nakazawae, V. parvula and V. ratti were isolated and identified. The four strains of Veillonella showed differences in MIC values for different antibiotics and biofilm-forming ability.

Research on smooth path planning method based on improved ant colony algorithm optimized by Floyd algorithm.

Aiming at the problems of slow convergence and easy fall into local optimal solution of the classic ant colony algorithm in path planning, an improved ant colony algorithm is proposed. Firstly, the Floyd algorithm is introduced to generate the guiding path, and increase the pheromone content on the guiding path. Through the difference in initial pheromone, the ant colony is guided to quickly find the target node. Secondly, the fallback strategy is applied to reduce the number of ants who die due to falling into the trap to increase the probability of ants finding the target node. Thirdly, the gravity concept in the artificial potential field method and the concept of distance from the optional node to the target node are introduced to improve the heuristic function to make up for the fallback strategy on the convergence speed of the algorithm. Fourthly, a multi-objective optimization function is proposed, which comprehensively considers the three indexes of path length, security, and energy consumption and combines the dynamic optimization idea to optimize the pheromone update method, to avoid the algorithm falling into the local optimal solution and improve the comprehensive quality of the path. Finally, according to the connectivity principle and quadratic B-spline curve optimization method, the path nodes are optimized to shorten the path length effectively.

Triple-functional injectable liposome-hydrogel composite enhances bacteriostasis and osteo/angio-genesis for advanced maxillary sinus floor augmentation.

Bone-grafting biological materials are commonly used to increase the height of the alveolar bone in the maxillary posterior region during maxillary sinus floor augmentation. However, there has been little research on the development of an injectable bone-grafting material with bacteriostatic, angiogenic, and osteogenic properties. In this work, we developed a triple-functional vancomycin/deferoxamine/dexamethasone (Van/DFO/Dex) liposome-hydrogel composite with desirable injectability. The release kinetics confirmed orderly sustained release of Van (a bacteriostat), DFO (a vascularised small molecule), and Dex (an osteogenic small molecule). In vitro findings demonstrated the favourable cytocompatibility and antibacterial ability of this composite against Staphylococcus aureus. Additionally, the angiogenic ability of human umbilical vein endothelial cells and osteogenic differentiation activity of MC3T3-E1 cells were enhanced. An in vivo bacteriostasis assay and rabbit maxillary sinus floor augmentation model corroborated the enhanced bacteriostasis and vascularised bone regeneration properties of this functionalised composite. Overall, the favourable injectability to be fit for the minimally invasive procedure, locally sustained release property, and prominent biological functions underscore the clinical potential of Van/DFO/Dex as an ideal bone-grafting material for irregular bone defect repairs, such as maxillary sinus floor augmentation.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I).

PURPOSE: As clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. METHODS: SLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). RESULTS: The median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. CONCLUSION: Central review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Micropipes in SiC Single Crystal Observed by Molten KOH Etching.

Micropipe, a "killer" defect in SiC crystals, severely hampers the outstanding performance of SiC-based devices. In this paper, the etching behavior of micropipes in 4H-SiC and 6H-SiC wafers was studied using the molten KOH etching method. The spectra of 4H-SiC and 6H-SiC crystals containing micropipes were examined using Raman scattering. A new Raman peak accompanying micropipes located near -784 cm-1 was observed, which may have been induced by polymorphic transformation during the etching process in the area of micropipe etch pits. This feature may provide a new way to distinguish micropipes from other defects. In addition, the preferable etching conditions for distinguishing micropipes from threading screw dislocations (TSDs) was determined using laser confocal microscopy, scanning electron microscopy (SEM) and optical microscopy. Meanwhile, the micropipe etching pits were classified into two types based on their morphology and formation mechanism.

Aldehyde dehydrogenase 1B1 is a potential marker of colorectal tumors.

Colorectal cancer (CRC) is common worldwide. Aldehyde dehydrogenase 1B1 (ALDH1B1), a member of the ALDH1 family, serves as a biomarker for cancer stem cells. We hypothesized that ALDH1B1 expression is associated with colorectal tumors. Immunohistochemistry was used to detect ALDH1B1 expression across a commercial colorectal tissue microarray. The signal intensities of the positively stained tissues were expressed using the mean integrated optical density (mean IOD). We also analyzed ALDH1B1 mRNA expression in the Oncomine database. The associations between ALDH1B1 expression and CRC stage and prognosis were then evaluated using the web-based tools, GEPIA and UALCAN. Analysis of the tissue microarray revealed that the expression of ALDH1B1 was significantly higher in colorectal adenomas and colorectal adenocarcinoma (IOD/area values=0.117±0.070 and 0.168±0.0168, respectively) compared with normal and cancer-adjacent tissues (IOD/area values=0.051±0.028 and 0.068±0.053). For samples collected in the hospital, ALDH1B1 was highly expressed in the adenoma (IOD/area=0.103±0.054) and CRC (IOD/area=0.116±0.059) tissues compared with the cancer-adjacent tissues (IOD/area=0.066±0.024, p<0.05). The expression of ALDH1B1 in tissues from two resources was not found to be significantly associated with CRC stage. In Oncomine, ALDH1B1 mRNA expression was increased in the colorectal tumor tissues compared with the normal colorectal tissues (p=0.024) and its expression was independent of CRC stage and prognosis (p<0.05). Thus, while the protein and mRNA expression of ALDH1B1 suggests that it is a potential marker of colorectal tumors, its expression is independent of CRC stage and prognosis.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Identification and Validation of Novel Serum Autoantibody Biomarkers for Early Detection of Colorectal Cancer and Advanced Adenoma.

Background: Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC. Methods: Combined with CRC-associated autoantibodies discovered by serological proteome and multiplex analyses, 26 predefined autoantibodies were evaluated in 315 samples (130 CRCs, 75 advanced adenomas, and 110 healthy controls) by protein microarray analysis. Autoantibodies with potential detection value were verified by enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the accuracy of the biomarkers. Results: Four serum autoantibodies (ALDH1B1, UQCRC1, CTAG1, and CENPF) showed statistically different levels between patients with advanced neoplasm (CRC or advanced adenoma) and controls in microarray analysis, which were validated by ELISAs. Among the four biomarkers, the ALDH1B1 autoantibody showed the highest detection value with area under the curve (AUC) values of 0.70 and 0.74 to detect CRC and advanced adenoma with sensitivities of 75.68 and 62.31% and specificities of 63.06 and 73.87%, respectively. By combining the four biomarkers, the performance was improved with an AUC of 0.79 to detect CRC and advanced adenomas. Conclusion: The ALDH1B1 autoantibody has a good potential for early detection of CRC and advanced adenoma, and measuring serum autoantibodies against tumor-associated antigens may improve detection of early CRC.

Autoantibodies as biomarkers for colorectal cancer: A systematic review, meta-analysis, and bioinformatics analysis.

Colorectal cancer is a very common cancer worldwide. Serum tumor-associated autoantibodies (TAAbs), especially the anti-p53 autoantibody, may be promising biomarkers to detect early-stage colorectal cancer. This study aimed to identify all known autoantibodies and their value in colorectal cancer diagnosis, as well as exploring the underlying connections and mechanisms through a bioinformatics analysis. Databases were used to select available articles of TAAbs in colorectal cancer. In a meta-analysis of the anti-p53 autoantibody, the diagnostic odds ratio and area under the curve (AUC) of the summary receiver-operating characteristic (SROC) curve were calculated using Stata 12.0 and Meta-Disc 1.4. We identified 73 articles including 199 single autoantibodies and 42 multiple autoantibodies. The maximum value of Youden's index was 0.76, combining c-MYC, p53, cyclin B1, p62, Koc, IMP1, and survivin. The diagnostic odds ratio for anti-p53 autoantibody at all stages was 10.86 (95% CI 8.40, 14.06) with low heterogeneity (I2 = 40.3%) and the AUC of the SROC curve was 0.82. For the anti-p53 autoantibody in early-stage colorectal cancer, the diagnostic odds ratio was 4.82 (95% CI 2.95, 7.87) with heterogeneity (I2 = 7.9%) and the AUC of the SROC curve was 0.72. Eighty-seven autoantibodies were selected for bioinformatics analyses. We found that the most enriched functional terms and protein-protein interactions may relate to the mechanism of autoantibody generation. In summary, our study summarized the diagnostic value of TAAbs in colorectal cancer, either as single molecules or in combination. Bioinformatics analyses may be a new approach to explore the mechanism of autoantibody generation.

Beryllium inhibits apoptosis via mitochondria in beryllium-induced lung disease in the rat.

Objective: We aimed to determine whether beryllium toxicity was associated with mitochondria apoptosis pathway in SD rats. Methods: Thirty-two SD rats were given an intratracheal instillation dose of 10 g/l beryllium oxide (0.5 ml per rat). Additional 32 rats were given an intratracheal instillation dose of 0.9% normal saline (0.5 ml per rat). The percentage of apoptosis, mitochondrial membrane potential, the expression level of apoptosis related genes and proteins, including bcl2, Bax and Caspase-3 were detected. Results: The average of percentage of apoptosis, the expression of caspase-3, bax, and cytochrome c were decreased significantly in lung tissues from rats exposed to beryllium oxide compared to normal controls. The expression of bcl2 and ADP were increased significantly at 80 d after exposure. Conclusions: We conclude that inhibition of apoptosis by beryllium oxide involves mitochondrial apoptosis pathway in rat model of beryllium oxide-induced pulmonary disease.

Dust induces lung fibrosis through dysregulated DNA methylation.

Pneumoconiosis is a serious occupational disease that often occurs to coal workers with no early diagnosis and effective treatment at present. Diffuse pulmonary fibrosis is the major pathological change of pneumoconiosis, and its mechanism is still unclear. Epigenetics is involved in the development of many diseases, and it is closely associated with fibrosis. In this study, we investigated whether DNA methylation contributes to the pathogenesis of pulmonary fibrosis in pneumoconiosis. By exposure to coal dust or silica dust, we established the models of coal worker's pneumoconiosis (CWP), which showed an increased expression of COL-I, COL-III. We further found that DNMT1, DNMT3a, DNMT3b, MBD2, MeCP2 protein expression changed. Pretreatment with DNMT inhibitor 5-aza-dC reduced expression of COL-I, COL-III, and reduced pulmonary fibrosis. In summary, our results showed that DNA methylation contributes to dust-induced pulmonary fibrosis and that it may serve as a theoretical basis for testing DNA methyltransferase inhibitors in the treatment of CWP.

Complex ATP7B mutation patterns in Wilson disease and evaluation of a yeast model for functional analysis of variants.

Wilson disease (WD) is a rare autosomal recessive genetic disorder that is associated with various mutations in the ATP7B gene. Although ATP7B variants are frequently identified, the exact mutation patterns remain unknown because of the absence of pedigree studies, and the functional consequences of individual ATP7B variants remain to be clarified. In this study, we recruited 65 clinically diagnosed WD patients from 60 unrelated families. Pedigree analysis showed that besides several ATP7B homozygous variants (8/65, 12.3%), compound heterozygous variants (43/65, 66.2%) were present in the majority of WD patients. There were 20% of the patients had one (12/65, 18.5%) or multiple (1/65, 1.5%) variants in only a single allele, characterized by a high ratio of splicing or frameshift variants. Nine ATP7B variants were cloned into the pAG426GPD yeast expression vector to evaluate their functional consequences, and the results suggested different degrees of functional disruption from mild or uncertain to severe, consistent with the corresponding phenotypes. Our study revealed the complex ATP7B mutation patterns in WD patients and the applicability of a yeast model system to the evaluation of the functional consequences of ATP7B variants, which is essential for WD cases that are difficult to interpret.