Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. METHODS: Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. RESULTS: 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. CONCLUSIONS: Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.

Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.

Background: The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function. Materials and methods: Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV1, FVC, and FEV1/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results. Results: The MR results confirmed four taxa were found causally associated with the risk of IPF. Order Bifidobacteriales (OR=0.773, 95% CI: 0.610-0.979, p=0.033), Family Bifidobacteriaceae (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and Genus RuminococcaceaeUCG009 (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while Genus Coprococcus2 (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in Class Deltaproteobacteria, Order Desulfovibrionales, Family Desulfovibrionaceae, Class Verrucomicrobiae, Order Verrucomicrobiales and Family Verrucomicrobiaceae being the most prominent beneficial microbiota, while those in Family Lachnospiraceae, Genus Oscillospira, and Genus Parasutterella were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV1 and FVC on the increased abundance of six taxa (Phylum Actinobacteria, Class Actinobacteria, Order Bifidobacteriales, Family Bifidobacteriaceae, Genus Bifidobacterium, and Genus Ruminiclostridium9) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF. Conclusion: The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.

Phylogeography and population structure of Lagocephalus spadiceus (Richardson, 1845) (Tetraodontiformes, Tetraodontidae) in the South China Sea.

The climate fluctuations during the Late Pleistocene significantly influenced the phylogeographic structure and historical dynamics of marine fishes in the marginal seas of the western Pacific Ocean. The puffer fish, Lagocephalus spadiceus, holds substantial nutritional and economic value in the South China Sea. To investigate the demographic history and population structure of the L. spadiceus, the mitochondrial DNA COI and Cyt b gene datasets from 300 individuals across eight populations in the South China Sea were sequenced. Our findings revealed high haplotype diversity (0.874 ± 0.013) and low nucleotide diversity (0.00075 ± 0.00058). The phylogenetic tree and haplotype networks revealed no significant genetic differentiation along the northern coast of South China Sea. Neutrality tests, mismatch distribution analyses, and Bayesian skyline plots suggested that L. spadiceus underwent population expansion during the Late Pleistocene. Both ocean currents and climate change significantly influenced the geographical distribution and genetic population structure of L. spadiceus.

The efficacy of modified contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) using Sonazoid in diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.

Background: The contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) is an algorithm for the diagnosis of hepatocellular carcinoma (HCC) in high-risk populations. Previous studies have shown the algorithm to have high specificity and moderate sensitivity. Nevertheless, it is designated for utilization solely with blood pool contrast agents. Sonazoid, a contrast agent that combines blood pools and Kupffer cells properties, has recently gained approval for marketing in an increased number of countries. Enhanced sensitivity in diagnosing HCC may be achieved through the distinctive Kupffer phase (KP) exhibited by Sonazoid. Certain academics have suggested the modified CEUS LI-RADS using Sonazoid. The main criteria of mild and late (≥60 seconds) washout in CEUS LI-RADS LR-5 were replaced by KP (>10 minutes) defects as the primary criteria. The purpose of this research was to evaluate the effectiveness of the modified CEUS LI-RADS using Sonazoid in diagnosing HCC. Methods: Original studies on Sonazoid and CEUS LI-RADS were searched in the PubMed, Embase, Cochrane Library, and Web of Science databases until 13 July 2023, with no restrictions on language. We enrolled studies that applied Sonazoid for CEUS in patients at high risk of HCC and modified CEUS LI-RADS for the diagnosis of intrahepatic nodules. Meta-analyses, evaluations, case studies, correspondences, remarks, and summaries of conferences were excluded. Additionally, studies that fell outside the scope of this study and contained data on the same patients were also excluded. We evaluated the quality of research by employing the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A bivariate mixed effects model was utilized to conduct a meta-analysis, summarizing the sensitivity and specificity in the diagnosis of HCC. The investigation of potential factors contributing to study heterogeneity was conducted using meta-regression analysis. Results: Out of the 103 studies screened, 6 studies (835 lesions) were included in the final results. Modified CEUS LR-5 exhibited a sensitivity of 0.77 [95% confidence interval (CI): 0.70-0.82; I2=71.98%; P=0.00] and a specificity of 0.88 (95% CI: 0.83-0.92; I2=0.00; P=0.47) for HCC diagnosis, with heterogeneity in sensitivity. The presence of heterogeneity in the study was found to have a significant association with factors such as the study design, the number of image reviewers, the proportion of cirrhosis, the proportion of other non-HCC malignancies (OM) cases, and the type of reference standard (P≤0.05). Conclusions: The modified CEUS LI-RADS LR-5 categorization demonstrates a reasonable level of sensitivity 0.77, but an insufficient level of specificity 0.88 when diagnosing HCC. KP defects cannot be used as a primary feature in the diagnosis of HCC by CEUS LI-RADS, perhaps as an ancillary feature.

ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.

Construction of novel Ag/AgI/Bi4Ti3O12 plasmonic heterojunction: A study focusing on the performance and mechanism of photocatalytic removal of tetracycline.

As a result of the insufficient absorption of visible light, the application of Bi4Ti3O12 in the field of photocatalysis is limited. Ag/AgI was uniformly modified on the surface of the nanoflower bulb of Bi4Ti3O12 by simple precipitation method and photodeposition. The fabricated Ag/AgI/Bi4Ti3O12 obtained an ultra-high tetracycline (TC) removal rate under visible light irradiation. And the synergetic effects caused by the surface plasmon resonance (SPR) effect of Ag, the photosensitivity of AgI and the p-n heterojunction are the key to improving the photocatalytic performance of materials. Besides, four plausible photodegradation pathways of TC were proposed and its intermediates were evaluated for toxicity, showing a significant decrease in toxicity after photoreaction.

Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer.

BACKGROUND: Structural variations (SVs) are common genetic alterations in the human genome. However, the profile and clinical relevance of SVs in patients with hereditary breast and ovarian cancer (HBOC) syndrome (germline BRCA1/2 mutations) remains to be fully elucidated. METHODS: Twenty HBOC-related cancer samples (5 breast and 15 ovarian cancers) were studied by optical genome mapping (OGM) and next-generation sequencing (NGS) assays. RESULTS: The SV landscape in the 5 HBOC-related breast cancer samples was comprehensively investigated to determine the impact of intratumor SV heterogeneity on clinicopathological features and on the pattern of genetic alteration. SVs and copy number variations (CNVs) were common genetic events in HBOC-related breast cancer, with a median of 212 SVs and 107 CNVs per sample. The most frequently detected type of SV was insertion, followed by deletion. The 5 HBOC-related breast cancer samples were divided into SVhigh and SVlow groups according to the intratumor heterogeneity of SVs. SVhigh tumors were associated with higher Ki-67 expression, higher homologous recombination deficiency (HRD) scores, more mutated genes, and altered signaling pathways. Moreover, 60% of the HBOC-related breast cancer samples displayed chromothripsis, and 8 novel gene fusion events were identified by OGM and validated by transcriptome data. CONCLUSIONS: These findings suggest that OGM is a promising tool for the detection of SVs and CNVs in HBOC-related breast cancer. Furthermore, OGM can efficiently characterize chromothripsis events and novel gene fusions. SVhigh HBOC-related breast cancers were associated with unfavorable clinicopathological features. SVs may therefore have predictive and therapeutic significance for HBOC-related breast cancers in the clinic.

Effects of polyethylene microplastics stress on soil physicochemical properties mediated by earthworm Eisenia fetida.

Microplastics (MPs) are widely distributed in soil environments, but their ecological risks are not fully understood. To fill this knowledge gap, incubation experiments were conducted to explore the physiological response of Eisenia foetida (E. fetida) to polyethylene MP stress and its effects on soil physicochemical properties. E. fetida was incubated in soils amended with MPs of two particle sizes (13 µm and 130 µm) at six concentrations (0, 1, 3, 6, 10 and 20 g MPs·kg-1 soil) under laboratory conditions. The toxicity of 13 µm MPs on the growth and survival of E. fetida was greater than that of 130 µm MPs. Excessive reactive oxygen species accumulation induced by high MP concentrations decreased superoxide dismutase activity and increased malondialdehyde content. Soil pH increased significantly in the 130 µm treatments. MPs increased the contents of soil organic carbon and available potassium. However, the presence of MPs did not significantly alter available phosphorus or nitrate nitrogen content. MP contamination in soil may have adverse impacts on the growth of earthworms, induce oxidative stress in earthworms, and change soil physicochemical properties. In addition, the effects of MPs are size-dependent and dose-dependent. This study provides new evidence for the ecological risks of MP pollution in the earthworm-soil systems.

Di-aldehyde tunicate cellulose nanocrystal (D-tCNC) aerogels for drug delivery: Effect of D-tCNC composition on aerogel structure and release properties.

Aerogels as drug carriers have the characteristics of a large specific surface area, high porosity and an elastic skeleton structure. Compared with traditional drug carriers, the use of aerogels as drug carriers can avoid the complexity of drug delivery and improve the efficiency of drug loading. In this work, the oxidation of tunicate cellulose nanocrystals (tCNCs) with NaIO4 was used to prepare di-aldehyde tunicate cellulose nanocrystals (D-tCNCs). Tetracycline (TC) was used as a drug model and pH-responsive drug-loaded aerogels were prepared by the Schiff base reaction between TC and the aldehyde group on D-tCNCs. The chemical structure, crystallinity, morphology, compression properties, porosity, swelling rate and drug loading properties were investigated by FT-IR, XRD, SEM and universal testing machines. The results showed that the porosity and equilibrium swelling ratio of the D-tCNC-TC aerogels were 95.87 % and 17.52 g/g, respectively. The stress of the D-tCNC-TC aerogel at 15 % compression was 0.07 MPa. Moreover, the analysis of drug-loaded aerogels indicated that the drug loading and encapsulation rates of D-tCNC-TC aerogels were 16.86 % and 78.75 %, respectively. In in vitro release experiments, the cumulative release rate of drug-loaded aerogel at pH = 1.2 and pH = 7.4 was 87.5 % and 79.3 %, respectively. These results indicated that D-tCNC-TC aerogels have good drug loading capacity and are pH-responsive in the pH range of 1.2 to 7.4. The prepared D-tCNC-TC aerogels are expected to be applied in drug delivery systems.

Organic phosphorus levels change the hyphosphere phoD-harboring bacterial community of Funneliformis mosseae.

The phoD-harboring bacterial community is responsible for organic phosphorus (P) mineralization in soil and is important for understanding the interactions between arbuscular mycorrhizal (AM) fungi and phosphate-solubilizing bacteria (PSB) at the community level for organic P turnover. However, current understanding of the phoD-harboring bacterial community associated with AM fungal hyphae responses to organic P levels remains incomplete. Here, two-compartment microcosms were used to explore the response of the phoD-harboring bacterial community in the hyphosphere to organic P levels by high-throughput sequencing. Extraradical hyphae of Funneliformis mosseae enriched the phoD-harboring bacterial community and organic P levels significantly altered the composition of the phoD-harboring bacterial community in the Funneliformis mosseae hyphosphere. The relative abundance of dominant families Pseudomonadaceae and Burkholderiaceae was significantly different among organic P treatments and were positively correlated with alkaline phosphatase activity and available P concentration in the hyphosphere. Furthermore, phytin addition significantly decreased the abundance of the phoD gene, and the latter was significantly and negatively correlated with available P concentration. These findings not only improve the understanding of how organic P influences the phoD-harboring bacterial community but also provide a new insight into AM fungus-PSB interactions at the community level to drive organic P turnover in soil.

Structural characterization and in vitro fermentation properties of polysaccharides from Polygonatum cyrtonema.

Polysaccharides, the major active ingredient and quality control indicator of Polygomatum cyrtonema are in need of elucidation for its in vitro fermentation characteristics. This study aimed to investigate the structural characteristics of the homogeneous Polygomatum cyrtonema polysaccharide (PCP-80 %) and its effects on human intestinal bacteria and short chain fatty acids (SCFAs) production during the in vitro fermentation. The results revealed that PCP-80 % was yielded in 10.44 % and the molecular weight was identified to be 4.1 kDa. PCP-80 % exhibited a smooth, porous, irregular sheet structure and provided good thermal stability. The analysis of Gas chromatograph-mass spectrometer (GC-MS) suggested that PCP-80 % contained six glycosidic bonds, with 2,1-linked-Fruf residues accounted for a largest proportion. Nuclear magnetic resonance (NMR) provided additional evidence that the partial structure of PCP-80 % probably consists of →1)-ß-D-Fruf-(2 â†’ as the main chain, accompanied by side chains dominated by →6)-ß-D-Fruf-(2→. Besides, PCP-80 % promoted the production of SCFAs and increased the relative abundance of beneficial bacteria such as Megamonas, Bifidobacterium and Phascolarctobacterium during in vitro colonic fermentation, which changed the composition of the intestinal microbiota. These findings indicated that Polygomatum cyrtonema polysaccharides were able to modulate the structure and composition of the intestinal bacteria flora and had potential probiotic properties.

Heavy Metals in Surface Sediment of Plateau Lakes in Tibet, China: Occurrence, Risk Assessment, and Potential Sources.

Tibetan Plateau lakes have high ecological value and play a crucial role in maintaining ecological balance. This research aimed to study the pollution characteristics, ecological risk, and potential sources of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface sediments of 12 Tibetan Plateau lakes. The results of the toxicity risk index (TRI) showed that only Gongzhu Tso (28.09) and La' ang Tso (20.25) had heavy metals that could pose a very high risk of toxicity to aquatic organisms. Hg posed the highest potential ecological risk to aquatic organisms. Based on the results of multiple analyses, we inferred that the contents of Cr, Cu, Hg, and Ni in sediments of Tibetan lakes were influenced by industrial and agricultural development; Cd, Pb, and Zn were influenced by transport and atmospheric transport; and As was derived from geothermal activity and rock weathering.

Levels and health risk assessment of potential toxic elements in three dominant fish species from the Beibu Gulf, South China Sea.

In this study, eight potential toxic elements (PTEs) and stable isotope ratios (δ13C and δ15N) were analyzed in three dominant fish species of the Beibu Gulf, namely Saurida tumbil, Pennahia macrocephalus and Upeneus sulphureus. The mean contents (mg/kg, dry weight) of As, Cd, Cr, Cu, Mn, Ni, Pb and Zn in the three species of fish were 10.94, 0.11, 0.55, 2.00, 5.80, 0.47, 0.39, 41.70, respectively. Cr, Mn and Pb showed potential biomagnification effects in fish bodies while Cu and Zn were biodiluted through the food chain. The results of the health risk assessment showed that the total hazard quotient (THQ) ranged from 0.11 to 0.32 and 1.34 to 1.70 and the total carcinogenic risk (TCR) ranged from 5.44 × 10-4 to 1.35 × 10-3 and 6.35 × 10-3 to 1.57 × 10-2 for adults and children, respectively. These results suggest that consumption of the three fish species by adults lead to carcinogenic health risks and consumption of the three fish species by children would result in significant adverse health effects.

Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial fibrosis is the main factor causing ventricular wall stiffness and heart failure in DCM. Early control of myocardial fibrosis in DCM is of great significance to prevent or postpone the progression of DCM to heart failure. A growing body of evidence suggests that cardiomyocytes, immunocytes, and endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, the main participants in collagen production, are situated in the most central position in cardiac fibrosis. In this review, we systematically elaborate the source and physiological role of myocardial fibroblasts in the context of DCM, and we also discuss the potential action and mechanism of cardiac fibroblasts in promoting fibrosis, so as to provide guidance for formulating strategies for prevention and treatment of cardiac fibrosis in DCM.

Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly.

The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food.

Combinatorial metabolic engineering and tolerance evolving of Escherichia coli for high production of 2'-fucosyllactose.

2'-Fucosyllactose (2'-FL) is an important functional ingredient of advanced infant formula. Here, Escherichia coli MG1655 was engineered for achieving high 2'-FL production. The expressions of 2'-FL synthesis pathway genes were finely regulated with single or multi copies according to rate-limiting enzyme diagnosis. On this basic, the branch pathway genes were deleted, and the overexpression of the 2'-FL efflux protein SetA and the fructose-1,6-bisphosphatase GlpX were tuned. The resulting strain produced 46.06 ± 1.28 g/L 2'-FL in a 5-L fermenter. Furtherly, adaptive laboratory evolution was conducted. A rpoC gene mutation was obtained which could improve the cell tolerance and the 2'-FL production up to 61.06 ± 1.93 g/L, with the highest productivity of 1.70 g/L/h among E. coli strains by now. Taken together, this work provides a combinatorial strategy to improve 2'-FL accumulation including rational fine-tuning pathway genes expressions and irrational adaptive laboratory evolution. This study should be helpful for constructing high level 2'-FL producers.

MR imaging phenotypes and features associated with pathogenic mutation to predict recurrence or metastasis in breast cancer.

OBJECTIVES: Distant metastasis remains the main cause of death in breast cancer. Breast cancer risk is strongly influenced by pathogenic mutation.This study was designed to develop a multiple-feature model using clinicopathological and imaging characteristics adding pathogenic mutations associated signs to predict recurrence or metastasis in breast cancers in high familial risk women. METHODS: Genetic testing for breast-related gene mutations was performed in 54 patients with breast cancers. Breast MRI findings were retrospectively evaluated in 64 tumors of the 54 patients. The relationship between pathogenic mutation, clinicopathological and radiologic features was examined. The disease recurrence or metastasis were estimated. Multiple logistic regression analyses were performed to identify independent factors of pathogenic mutation and disease recurrence or metastasis. Based on significant factors from the regression models, a multivariate logistic regression was adopted to establish two models for predicting disease recurrence or metastasis in breast cancer using R software. RESULTS: Of the 64 tumors in 54 patients, 17 tumors had pathogenic mutations and 47 tumors had no pathogenic mutations. The clinicopathogenic and imaging features associated with pathogenic mutation included six signs: biologic features (p = 0.000), nuclear grade (p = 0.045), breast density (p = 0.005), MRI lesion type (p = 0.000), internal enhancement pattern (p = 0.004), and spiculated margin (p = 0.049). Necrosis within the tumors was the only feature associated with increased disease recurrence or metastasis (p = 0.006). The developed modelIincluding clinico-pathologic and imaging factors showed good discrimination in predicting disease recurrence or metastasis. Comprehensive model II, which included parts of modelIand pathogenic mutations significantly associated signs, showed significantly more sensitivity and specificity for predicting disease recurrence or metastasis compared to Model I. CONCLUSIONS: The incorporation of pathogenic mutations associated imaging and clinicopathological parameters significantly improved the sensitivity and specificity in predicting disease recurrence or metastasis. The constructed multi-feature fusion model may guide the implementation of prophylactic treatment for breast cancers at high familial risk women.

Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei.

The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). Additionally, different monosaccharide composition was exhibited due to diverse extraction methods. Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues.

Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer.

INTRODUCTION: Gastric cancer (GC)is the third leading cause of cancer-related deaths in China and immunotherapy emerging as a revolutionary treatment for GC recently. Tumor mutational burden (TMB) is a predictive biomarker of immunotherapy in multiple cancers. However, the prognostic significance and subtype of TMB in GC is not fully understood. OBJECTIVES: This study aims to evaluate the prognostic value of TMB in Chinese GC and further classify TMB-high GC (GCTMB-H) patients combing with mutational signatures. METHODS: Genomic profiling of 435 cancer-gene panel was performed using 206 GC samples from Chinese people. Actionable genetic alterations were compared across all the samples to generate actionable subtyping. The prognostic value of TMB in Chinese GC was evaluated. Mutational signatures were analyzed on TMB-H subtype to stratify the prognosis of TMB. Transcriptomic analysis was applied to compare the distributed immunocytes among different subtypes. RESULTS: 88.3% (182/206) of GC samples had at least one mutation, while 45.1% (93/206) had at least one somatic copy number alteration (SCNA). 29.6% (61/206) of GC samples were TMB-H, including 13 MSI-H and 48 MSS tumors. According to distinct genetic alteration profiles of 69 actionable genes, we classified GC samples into eight molecular subtypes, including TMB-H, ERBB2 amplified, ATM mutated, BRCA2 mutated, CDKN2A/B deleted, PI3KCA mutated, KRAS mutated, and less-mutated subtype. TMB-H subtype presented a remarkable immune-activated phenotype as determined by transcriptomic analysis that was further validated in the TCGA GC cohort. GCTMB-H patients exhibited significantly better survival (P = 0.047). But Signature 1-high GCTMB-H patients had relatively worse prognosis (P = 0.0209, HR = 2.571) than Signature 1-low GCTMB-H patients from Chinese GC cohort, also validated in TCGA GC cohort, presenting highly activated carbohydrate, fatty acid or lipid metabolism. CONCLUSION: The Signature 1-high GCTMB-H could be a marker of poor prognosis and is associated with metabolism disorder.

Halogenated organic pollutants (HOPs) in marine fish from the Beibu Gulf, South China Sea: Levels, distribution, and health risk assessment.

Six marine fish species, collected from the Beibu Gulf were statistically analyzed for polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethanes (DDTs). The concentrations of ∑14PBDEs, ∑26PCBs, and ∑6DDTs ranged from 11.8-1431, 8.74-495, and 9.47-1263 ng g-1 lipid weight (lw), respectively. In general, PBDEs were the predominant halogenated organic pollutants (HOPs) in the Beibu Gulf. The homologues profiles of Mugil cephalus and Trichiurus nanhaiensis differed from other four species. For example, the contributions of deca-BDEs in M. cephalus (14 %) and T. nanhaiensis (1 %) were lower than other four species (56 %). The ratio of (DDE + DDD)/ΣDDTs in all samples was >0.5, indicating that DDTs were mainly derived from historical residues. Intakes of HOPs through the consumption of the marine fish from the study areas might not subject residents of the coastal areas in the Beibu Gulf to health risks.