Systematic proteomics analysis revealed different expression of laminin interaction proteins in breast cancer: lower in luminal subtype and higher in claudin-low subtype.

Background: Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets. Methods: Protein expression level in breast cancer tissues and para-carcinoma tissues were detected by Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology and further screened through Gene Expression Profiling Interactive Analysis (GEPIA) database. Cellular components, protein domain and Reactome pathway analysis were performed to screen functional targets. Abnormal expression levels of functional targets were validated by Oncomine database, quantitative real time polymerase chain reaction (qRT-PCR) and proteomics detection. Protein correlation analysis was performed to explain the abnormal expression levels of potential targets in breast cancer. Results: Overall, 207 and 207 proteins were up- and down-regulated, respectively, in breast cancer tissues, and approximately 50% were also detected in the GEPIA database. The overlapping proteins were mainly extracellular proteins containing epidermal growth factor-like domain in leukocyte adhesion molecule (EGF-Lam) domain and enriched in laminin interaction pathway. Moreover, the downregulated laminin interaction proteins could be functional targets, which were also validated through Oncomine-Richardson and Oncomine-Curtis database. However, the lower expression level of laminin interaction proteins only fit for luminal breast cancer cells with no or low metastasis ability because the proteins achieved higher expression level in more invasive claudin-low breast cancer cells. In addition, when compared with corresponding in situ carcinoma tissues, above-mentioned proteins also showed higher expression levels in invasive carcinoma tissues. Finally, we have revealed the negative correlation between the laminin interaction proteins and the claudins. Conclusions: The laminin interaction protein, especially for laminins with ß1 and γ1 subunits and their integrin receptors with α1 and α6 subunits, showed lower expression levels in luminal breast cancer with no or lower metastatic ability, but showed higher expression levels in claudin-low breast cancer with higher metastatic ability; and their higher expression could be related to the low claudin expression.

Earth's early continental crust formed from wet and oxidizing arc magmas.

Formation of continental crust has shaped the surface and interior of our planet and generated the land and mineral resources on which we rely. However, how the early continental crust of Earth formed is still debated1-7. Modern continental crust is largely formed from wet and oxidizing arc magmas at subduction zones, in which oceanic lithosphere and water recycle into the mantle8-10. The magmatic H2O content and redox state of ancient rocks that constitute the early continental crust, however, are difficult to quantify owing to ubiquitous metamorphism. Here we combine two zircon oxybarometers11,12 to simultaneously determine magmatic oxygen fugacity (fO2) and H2O content of Archaean (4.0-2.5 billion years ago) granitoids that dominate the early continental crust. We show that most Archaean granitoid magmas were ≥1 log unit more oxidizing than Archaean ambient mantle-derived magmas13,14 and had high magmatic H2O contents (6-10 wt%) and high H2O/Ce ratios (>1,000), similar to modern arc magmas. We find that magmatic fO2, H2O contents and H2O/Ce ratios of Archaean granitoids positively correlate with depth of magma formation, requiring transport of large amounts of H2O to the lower crust and mantle. These observations can be readily explained by subduction but are difficult to reconcile with non-subduction models of crustal formation3-7. We note an increase in magmatic fO2 and H2O content between 4.0 and 3.6 billion years ago, probably indicating the onset of subduction during this period.

Optimum capture size of Trichiurus japonicus in the East China Sea.

Trichiurus japonicus is an economically valuable species in the East China Sea, whose allowable capture size varies with fishing effort in different years. To clarify the optimum capture size for T. japonicus in the East China Sea, we collected samples and data from T. japonicus targeting fishing gears such as trawls, canvas spreader stow nets and longlines from 2016 to 2020. We estimated growth and mortality parameters using the FiSAT II software, and calculated the size limit standards for capture. The results showed that the inflection point of anal length, the critical anal length and the anal length of one-year-old T. japonicus was 382.84, 397.12, and 216.05 mm, respectively. The anal length of maturity was 230.38 mm, and the minimum capture size (anal length) was 219.23 mm. Based on the yield per recruitment analysis using Beverton-Holt model, the current fishery reference points were under overfishing condition (tc=0.38 a, F=2.11), and the suggested optimum capture size was 364.64 mm. There would be a sharp decline of T. japonicus catches in the East China Sea if the suggested minimum capture size was substantially higher, which might be non-practical for local fishermen. Therefore, we suggested 220 mm as the capture size limit, which was close to the anal length of one-year-old fish and the anal length of maturity.

Phase Deflectometry for Defect Detection of High Reflection Objects.

A method for detecting the surface defects of high reflection objects using phase deflection is proposed. The abrupt change in the surface gradient at the defect leads to the change in the fringe phase. Therefore, Gray code combined with a four-step phase-shift method was employed to obtain the surface gradients to characterize the defects. Then, through the double surface illumination model, the relationship between illumination intensity and phase was established. The causes of periodic error interference were analyzed, and the method of adjusting the fringe width to eliminate it was proposed. Finally, experimental results showed the effectiveness of the proposed method.

[Heterogeneity of fork length-weight relationship for juvenile Engraulis japonius based on linear mixed-effects models]. / 基于线性混合效应模型的日本鳀幼鱼叉长-ä½“é‡å ³ç³»å¼‚è´¨æ€§.

In order to examine the growth heterogeneity of juvenile Engraulis japonicus, we conducted heterogeneity analysis of fork length-weight relationships of the species based on the samples of juvenile E. japonius from April to June 2019 collected from the coastal waters of Zhejiang Province by using the generalized linear model and 9 linear mixed-effect models. The results showed that the fork length of juvenile E. japonius was between 14-74 mm, with an average of 33 mm. The dominant fork length group was 21-50 mm. The weight range was 0.01-2.96 g, with an average of 0.28 g, and the dominant body weight group was 0.01-0.50 g. According to Akaike information criterion (AIC), the growth-fitting model with both months and regions random effects on the growth parameters a and b of juvenile E. japonius fitted best.The reliable prediction results was testified by the cross-validation. In the best model, the fixed value of growth parameter a was 0.24×10-5 and its estimated value did not fluctuate significantly, while the fixed value of b was 3.246 and the estimated value ranged from 3.206 to 3.272, indicating that juvenile E. japonius was under positive allometric growth. Our results suggested that month and region significantly affected the fork length-weight relationships of juvenile E. japonius.

Association between genetic polymorphism of heme oxygenase 1 promoter and neonatal hyperbilirubinemia: a meta-analysis.

Objective: The association between a (GT)n dinucleotide length polymorphism in the promoter region of heme oxygenase 1 (HMOX1) and the risk of neonatal hyperbilirubinemia remains controversial. This meta-analysis was, therefore, performed with aims to examine the correlation between the HMOX1 (GT)n repeat length polymorphism and neonatal hyperbilirubinemia susceptibility.Materials and methods: We searched the databases including PubMed, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), and Wanfang Data, with all reviewed studies published before 28 June 2018. After the evaluation of quality, we used RevMan to perform the meta-analyses. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the effect of HMOX1 gene promoter polymorphisms on the risk of neonatal hyperbilirubinemia.Results: Seven studies, involving 584 patients with neonatal hyperbilirubinemia and 1655 controls, were included. A statistically significant association was found between the HMOX1 (GT)n repeat length polymorphism and risk of neonatal hyperbilirubinemia under the allele (allele S vs. allele L: OR = 1.81, 95% CI = 1.22-2.67, p = .003), recessive (genotype SS vs. genotypes LS + LL: OR = 1.38, 95% CI = 1.02-1.86, p = .04), dominant (genotypes SS + LS vs. LL: OR = 1.37, 95% CI = 1.01-1.76, p = .01), and homozygous genetic models (genotype SS vs. genotype LL: OR = 1.47, 95% CI = 1.02-2.11, p = .003), but not under the heterozygous genetic model. Interestingly, subgroup analysis revealed that the cutoffs of the S allele < 25 showed significant associations in any of the five genetic models (allele S vs. allele L: OR = 2.26, 95% CI = 1.68-3.05, p < .00001; genotype SS vs. genotypes LS + LL: OR = 2.56, 95% CI = 1.41-4.65, p = .002; genotypes SS + LS vs. genotype LL: OR = 1.82, 95% CI = 1.28-2.59, p = .0009; genotype SS vs. genotype LL: OR = 3.09, 95% CI = 1.50-6.36, p = .002; genotype LS vs. genotype LL: OR = 1.64, 95% CI = 1.11-2.42, p = .01); however, this association was not observed in the cutoffs of the S allele ≥25.Conclusion: The results of this study indicate that there is a significant association between the HMOX1 (GT)n repeat length polymorphism and susceptibility to neonatal hyperbilirubinemia. Newborns carrying shorter (GT)n repeats in the HMOX1 gene promoter may have a higher risk of neonatal hyperbilirubinemia.

Characterization and functional analysis of slc7a11 gene, involved in skin color differentiation in the red tilapia.

Red tilapia has become more popular for aquaculture production in China in recent years. However, the pigmentation differentiation that has resulted from the process of genetic breeding and skin color variation during the overwintering period are the main problems limiting the development of commercial culture. The genetic basis of skin color differentiation is still not understood. Solute carrier family 7 member 11 (slc7a11) has been identified to be a critical genetic regulator of pheomelanin synthesis in the skin of mammals. However, little information is available about its molecular characteristics, expression, location and function in skin color differentiation of fish. In this study, three complete cDNA sequences (2159 bp, 2190 bp and 2249 bp) of slc7a11 were successfully isolated from Malaysian red tilapia, encoding polypeptides of 492, 525 and 492 amino acids respectively. Quantitative real-time PCR demonstrated that slc7a11 mRNA expression is high in the ventral skin of PR (pink with scattered red spots) fish. Immunofluorescence analysis revealed that xCT (the protein encoded by slc7a11) was concentrated mainly in the cytoplasm and nucleus of both the dorsal and ventral skin cells of fish. After RNA interference of slc7a11, slc7a11 and cbs mRNA expressions decreased, but the tyr mRNA expression increased in the skin of fish. Results suggest that slc7a11 plays an important role in skin color formation and differentiation of red tilapia through the melanogenesis pathway.

AMD3100 inhibits epithelial-mesenchymal transition, cell invasion, and metastasis in the liver and the lung through blocking the SDF-1α/CXCR4 signaling pathway in prostate cancer.

Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) have been found to be tightly correlated with the progression of prostate cancer (PC). In this study, we investigated the effects of an SDF-1α/CXCR4 inhibitor, AMD3100, on cell progression and metastasis potential of human PC cells. Human PC cell lines (LNCaP, PC3, and DU145) were cultured to detect SDF-1α/CXCR4, which showed higher SDF-1α and CXCR4 expression than the normal human prostate epithelial cell line, RWPE-1. AMD3100 was confirmed to be an inhibitor of SDF-1α, and to detect the effect of SDF-1α/CXCR4 inhibition on PC, PC cells were treated with AMD3100 or/and CXCR4 siRNA. The results suggested that inhibition of the SDF-1α/CXCR4 pathway could promote the E-cadherin level but inhibit the levels of invasion and migration of vimentin, N-cadherin and α5ß1 integrin. Finally, tumor formation in nude mice was conducted, and the cell experiment results were verfied. These data show that AMD3100 suppresses epithelial-mesenchymal transition and migration of PC cells by inhibiting the SDF-1α/CXCR4 signaling pathway, which provides a clinical target in the treatment of PC.

The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes.

OBJECTIVE: Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited. DESIGN AND METHODS: One hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees. RESULTS: Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands. CONCLUSIONS: Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.

Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway.

Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is known to exhibit anticancer properties against a variety of carcinomas. Previous experimental evidence suggests that lifestyle and dietary habits affect the risk of prostate cancer to a certain extent. As the effect of tangeretin on prostate cancer is unexplored, the present study investigated the effect of tangeretin on androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin reduced the cell viability of PC-3 cells in a dose- and time-dependent manner, with the half-maximal inhibitory concentration (IC50) observed at 75 µM dose following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be ~65 µM. Expression levels of the mesenchymal proteins including vimentin, cluster of differentiation 44 and Neural cadherin in PC-3 cells were reduced by tangeretin treatment, whereas those of the epithelial proteins, including Epithelial cadherin and cytokeratin-19 were upregulated. Treatment of PC-3 cells also resulted in the downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Therefore, it may be concluded that tangeretin induces reprogramming of epithelial-mesenchymal transition in PC-3 cells by targeting the PI3K/Akt/mTOR signaling pathway.

Chikusetsu (CHI) triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species (ROS) production.

The prostate cancer prognosis is still not fully understood. Chikusetsu saponin Iva (CHI), isolated from Aralia taibaiensis, shows anti-cancer and anti-inflammatory properties. Here, in our study, we attempted to explore the efficiency and the possible molecular mechanism by which CHI may suppress prostate cancer. CHI was found to inhibit prostate cancer cell proliferation and induce cell death without cytotoxicity in prostate normal cells. CHI resulted in intracellular reactive oxygen species (ROS) production, and induced apoptosis regulated by mitochondria in vitro studies. CHI-caused apoptosis was shown in both caspase-dependent and -independent manner, which released cyto-c, enhancing caspases expression and promoting apoptosis-inducing factors (AIF) as well as endonuclease G (Endo G) nuclear transfer, respectively. Moreover, in vivo study showed that prostate tumor was inhibited by CHI administration through apoptosis induction. Thus, the results illustrated that CHI might be an effective therapeutic strategy for prostate cancer treatment in future.

In-depth transcriptome analysis of Larimichthys polyactis, de novo assembly, functional annotation.

Larimichthys polyactis (small yellow croaker) is a commercially important marine benthic fish, and is the main catching target of fisheries in China, Japan and Korea. Researches across different fields have progressed the understanding of this species; however, no genomics studies of this fish have been reported so far. In this study, we performed de novo transcriptome sequencing of eight cDNA libraries from brain, gill, heart, intestine, liver, muscle, ovary, and testis tissues of L. polyactis. A total of 182,227,948 paired-end reads (>200bp) were generated, from which 134,439 transcripts were assembled. These transcripts yielded a total of 93,990 non-redundant transcripts (unigenes) that were assigned functional annotations based on BlastX searches (E-value<1×10-5) against the following databases: NCBI NR, Swiss-Prot, TrEMBL, CDD, Pfam, and COG. In addition, 12,539 simple sequence repeats (SSRs) were identified. Our study provides a valuable resource of L. polyactis transcriptomic data that are expected to be useful for gene expression and functional studies of L. polyactis.

A novel dual oxidase maturation factor 2 gene mutation for congenital hypothyroidism.

Congenital hypothyroidism (CH) is caused by thyroid hormone deficiency present at birth. DUOXA2 (dual oxidase maturation factor 2) is one of the prerequisites for thyroid hormone synthesis. The present study explored the novel mutations of DUOXA2 in CH patients. Genomic DNA was extracted from peripheral blood of 47 unrelated CH patients, their family members and 100 healthy controls. All 6 exons and their flanking sequences of the DUOXA2 gene were PCR amplified and sequenced. Sequencing results were compared with the standard. Compound heterozygosity with DUOXA2 gene mutations at c.413-414insA (Y138X) and c.738C>G (Y246X) was identified in one patient, and absent in 100 healthy controls. Among them, the c.413­414insA (Y138X) mutation was a novel one. The patient with the c.413-414insA (Y138X) mutation had mild CH symptoms. This study is the first to report a novel c.413-414insA (Y138X) mutation for CH, thereby expanding the mutational spectrum of the DUOXA2 gene.

Transurethral 2-microm laser in the treatment of urethral stricture.

OBJECTIVES: To evaluate the curative efficacy of transurethral 2-mum thulium laser urethrotomy in the treatment of urethral stricture. METHODS: Two hundred and thirty-eight patients suffering from urethral stricture, all male, aged 47.3 (36-58), underwent transurethral 2-mum thulium laser urethrotomy. The maximum flow rate (MFR), the international prostatic symptom score (IPSS) and the quality of life (QoL) were measured before operation, immediately following the removal of the catheter, and 3 and 6 months postoperatively. RESULTS: The surgery was performed for all the patients with no rectum injury, urine leakage or massive blood loss. All the patients got free urination immediately following the catheter removal with the mean MFR improved from (3.2 + or - 0.3) ml/s preoperatively to (16.7 + or - 3.1) ml/s, which kept steady to (18.7 + or - 2.9) and (19.2 + or - 2.8) ml/s, respectively 3 and 6 months after operation. IPSS significantly improved from 28.3 + or - 5.8 preoperatively to 7.1 + or - 1.9, 6.4 + or - 1.5 and 5.3 + or - 1.3, respectively when catheter removal and 3 and 6 months after operation. Also during the corresponding period, mean QoL improved from 5.4 + or - 1.1 to 1.1 + or - 0.3, 0.9 + or - 0.2 and 0.8 + or - 0.2. 195, patients got permanent uninterrupted urination without recurrence in the whole 6 months of follow-up. Forty-three patients got recurrence and seven patients encountered with incontinence 1-3 weeks (mean 13.8 days) after catheter removal, but they all got final cure after periodic urethral dilatation and physical exercise. CONCLUSIONS: Transurethral 2-mum thulium laser is safe and efficient in the treatment of urethral stricture.

Oxidative carboxylation of arylaldehydes with water by a sulfoxylalkyl-substituted N-heterocyclic carbene catalyst.

The N-Heterocyclic carbene-catalysed oxidative carboxylation of arylaldehydes with water successfully proceeded when a sulfoxylalkyl-substituted imidazolium salt was used as the catalyst. The reactions can be run in the absence of oxidant, and a variety of arylaldehydes having an electron-withdrawing group were converted to the corresponding carboxylic acids.

[Evaluation of effectiveness of intervention on risk factors for cerebrovascular disease in three cities of China].

OBJECTIVE: To evaluate the effects of community intervention on risk factors of cerebrovascular disease. METHODS: With cluster sampling, 2,586 and 2,723 women and men aged 35 to 74 were selected randomly as intervention cohort and control cohort, respectively, from about 300 thousand community population in Beijing, Shanghai and Changsha, during 1997 to 2000. Their blood pressure, levels of blood lipid, body mass index (BMI) were measured and status of smoking and alcohol consumption were surveyed as indices of evaluation. Health education for smoking quit, alcohol consumption restriction and reinforced treatment for diabetic and hypertensive patients were implemented in the intervention communities. And, 2,544 and 2,533 persons in the two cohorts responded three years after intervention, and then all the indices mentioned above were measure again for them. RESULTS: Average reduction in systolic blood pressure by 3.21 mm Hg and serum level of total cholesterol by 0.58 mmol/L was achieved in intervention cohort after intervention, but with 0.48 mmol/L increase in triglyceride. Average blood levels of both high density lipoprotein-cholesterol (HDL-C) and glucose increased in the two cohorts after intervention, but with 0.30 mmol/L net increase of blood glucose in control cohort. There was no significant difference in average increase of HDL-C between the two cohorts. BMI increased by 0.56 in control cohort, and no significant change in intervention cohort. Proportion of smoking decreased by 5.4% in men and 2.4% in women of intervention cohort, and no change in control cohort. CONCLUSION: Level of risk factors for cerebrovascular disease reduced significantly with community intervention.