2D Tantalum Disulfide Reduction Strategy Customized Ta2O5/rGO Heterointerface Aerogel Toward Boosting Electromagnetic Wave Absorption and Flame Retardancy.

The exceptional and substantial electron affinity, as well as the excellent chemical and thermal stability of transition metal oxides (TMOs), infuse infinite vitality into multifunctional applications, especially in the field of electromagnetic wave (EMW) absorption. Nonetheless, the suboptimal structural mechanical properties and absence of structural regulation continue to hinder the advancement of TMOs-based aerogels. Herein, a novel 2D tantalum disulfide (2H-TaS2) reduction strategy is demonstrated to synthesize Ta2O5/reduced graphene oxide (rGO) heterointerface aerogels with unique characters. As the prerequisite, the defects, interfaces, and configurations of aerogels are regulated by varying the concentration of 2H-TaS2 to ensure the Ta2O5/rGO heterointerface aerogels with appealing EMW absorption properties such as a minimum reflection loss (RLmin) of -61.93 dB and an effective absorption bandwidth (EAB) of 8.54 GHz (7.80-16.34 GHz). This strategy provides valuable insights for designing advanced EMW absorbers. Meanwhile, the aerogel exhibits favorable thermal insulation performance with a value of 36 mW m-1 K-1, outstanding fire resistance capability, and exceptional mechanical energy dissipation performance, making it promising for applications in the aerospace industry and consumer electronics devices.

Neural dynamics and coupling underlying uncertain anticipatory conflicts in anxious individuals.

Anticipation plays an important role in cognitive control and related psychiatric disorders such as anxiety. However, anticipation processing of conflicts in anxious individuals and the underlying brain mechanisms remain unknown. Using a newly designed cue-flanker task, we observed faster responses to congruent flankers with certain cues in individuals with high trait anxiety (HTA) than those with low trait anxiety (LTA). Microstate analyses revealed less occurrence of cue-evoked microstates in HTA than LTA. Importantly, the less occurrence of specific state was correlated to the larger flanker effect in HTA, suggesting that deficient conflict control in anxiety is associated with abnormal vigilance-related dynamic processing during anticipation. Delta-beta coupling at anticipation stage mediated the association between the level of anxiety and reaction time in conflict processing with uncertain cues in HTA, suggesting the mediatory role of delta-beta coupling in anticipatory conflict processing of anxious individuals. These results suggest hyperactive anticipatory processing of goal-relevant information for the upcoming conflict in anxious individuals. Our findings provide neurocognitive evidence for altered anticipatory cognitive control in anxious individuals and have important implications for diagnosis and treatment of anxiety-related disorders.

Polarized light compass-aided inertial navigation under discontinuous observations environment.

In recent years, integrated polarized light/inertial heading measurement systems have been widely used to obtain autonomous heading measurements of small unmanned combat platforms in the case of satellite navigation rejection. However, existing polarized light/inertial heading measurement systems have certain limitations. For example, they can only measure the heading angle in environments where continuous observations can be obtained. When encountering a complex environment with trees and/or tall buildings, the measured heading angle will contain sharp noise which greatly affects its accuracy. In particular, when encountering an underpass, it will lead to the complete loss of lock of the polarized light compass signal. Therefore, for the problem of sharp noise arising from a complex environment, a robust Cubature Kalman filter (CKF) data-fusion algorithm is proposed and verified by experiments. It is proved that the robust CKF algorithm has a certain ability to filter out the effects of poor measurements. After application of the robust CKF algorithm, the Root Mean Square Error (RMSE) of the heading angle reaches 0.3612°. This method solves the problem of low precision and poor stability of the polarized light/inertial system when high buildings and/or trees are contained in a complex environment. Next, in view of the problem that the polarized light compass signal is completely lost due to passing through an underground passage, a random forest regression (RFR) neural network model is established and introduced into the combined system. Simulated and outdoor experiments are carried out to verify the designed model using data obtained with a vehicle. The RMSE of the heading angle obtained in the experiment is 1.1894°, which solves the problem that the polarized light/inertial system cannot utilize discontinuous observations when attempting to detect the carrier heading angle.

Proteomic characteristics of PM2.5-induced differentially expressed proteins in k-ras-silenced HBE cells.

The human bronchial epithelial cells (HBE) and K-ras-silenced HBE cells were treated with fine particulate matter (PM2.5) samples from Taiyuan for 24 h. To screen the proteomic characteristics of PM2.5-induced differentially expressed proteins (DEPs), the Q Exactive mass spectrometer was used. Gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) analysis, functional prediction, protein-protein interaction (PPI) network analysis, and visualization of differential protein interactions were performed. 251 DEPs in K-ras silenced cells and 535 DEPs in normal HBE cells were identified, respectively. KEGG analysis showed that the differentially expressed proteins of PM2.5-treated cells were related to the biosynthesis of ribosomes, antibiotics, and amino acids. On the other hand, K-ras silenced cells were related to metabolic pathways, RNA transport, and DNA replication. Through the construction of a PPI network, the top 10 hub proteins were screened from the two cell groups, among which MRPL13, RPS20, and EIF1AX were of great significance. Our results indicated that the K-ras gene plays an important role in PM2.5-induced DEPs, and the findings provide a scientific basis for the further study of PM2.5 toxic mechanisms and biomarkers.

Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells.

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved in endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, have not been completely elucidated. In the present study, we identified orphan nuclear receptor Nur77 as a novel regulator in controlling inflammasome activation in vascular endothelial cells (ECs). We demonstrated that LPS-induced inflammasome activation was significantly inhibited by ectopic overexpression of Nur77, predominantly through transcriptional suppression of caspase-1 expression in vascular ECs. Consistent with this observation, we found that LPS-induced inflammasome activation was significantly augmented in lung ECs isolated from Nur77-knockout mice. Mechanistically, we showed that Nur77-induced inhibition of caspase-1 expression was due to an inhibition of IRF1 (IFN regulatory factor 1) expression and its subsequent binding to the caspase-1 promoter. Importantly, in a mouse model of LPS-induced ALI, Nur77 knockout led to a marked activation of caspase-1 in the lung, increased alveolar and circulating IL-1ß levels, and exacerbated ALI, all of which were substantially inhibited by administration of caspase-1 inhibitor. Together, our results support the presence of an important role for Nur77 in controlling inflammasome activation in vascular ECs and suggest that Nur77 could be a novel therapeutic target for the treatment of human diseases associated with aberrant inflammasome activation, such as ALI and atherosclerosis.

Tissue-specific study across the stem of Taxus media identifies a phloem-specific TmMYB3 involved in the transcriptional regulation of paclitaxel biosynthesis.

Taxus stem barks can be used for extraction of paclitaxel. However, the composition of taxoids across the whole stem and the stem tissue-specificity of paclitaxel biosynthesis-related enzymes remain largely unknown. We used cultivated Taxus media trees for analyses of the chemical composition and protein of major stem tissues by an integrated metabolomic and proteomic approach, and the role of TmMYB3 in paclitaxel biosynthesis was investigated. The metabolomic landscape analysis showed differences in stem tissue-specific accumulation of metabolites. Phytochemical analysis revealed that there is high accumulation of paclitaxel in the phloem. Ten key enzymes involved in paclitaxel biosynthesis were identified, most of which are predominantly produced in the phloem. The full-length sequence of TmMYB3 and partial promoter sequences of five paclitaxel biosynthesis-related genes were isolated. Several MYB recognition elements were found in the promoters of TBT, DBTNBT and TS. Further in vitro and in vivo investigations indicated that TmMYB3 is involved in paclitaxel biosynthesis by activating the expression of TBT and TS. Differences in the taxoid composition of different stem tissues suggest that the whole stem of T. media has potential for biotechnological applications. Phloem-specific TmMYB3 plays a role in the transcriptional regulation of paclitaxel biosynthesis, and may explain the phloem-specific accumulation of paclitaxel.

Omic analysis of the endangered Taxaceae species Pseudotaxus chienii revealed the differences in taxol biosynthesis pathway between Pseudotaxus and Taxus yunnanensis trees.

BACKGROUND: Taxol is an efficient anticancer drug accumulated in Taxus species. Pseudotaxus chienii is an important member of Taxaceae, however, the level of six taxoids in P. chienii is largely unknown. RESULTS: High accumulation of 10-DAB, taxol, and 7-E-PTX suggested that P. chienii is a good taxol-yielding species for large-scale cultivation. By the omics approaches, a total of 3,387 metabolites and 61,146 unigenes were detected and annotated. Compared with a representative Taxus tree (Taxus yunnanensis), most of the differentially accumulated metabolites and differential expressed genes were assigned into 10 primary and secondary metabolism pathways. Comparative analyses revealed the variations in the precursors and intermediate products of taxol biosynthesis between P. chienii and T. yunnanensis. Taxusin-like metabolites highly accumulated in P. chienii, suggesting a wider value of P. chienii in pharmaceutical industry. CONCLUSIONS: In our study, the occurrence of taxoids in P. chienii was determined. The differential expression of key genes involved in the taxol biosynthesis pathway is the major cause of the differential accumulation of taxoids. Moreover, identification of a number of differentially expressed transcription factors provided more candidate regulators of taxol biosynthesis. Our study may help to reveal the differences between Pseudotaxus and Taxus trees, and promote resource utilization of the endangered and rarely studied P. chienii.

A systematic review and meta-analysis of nab-paclitaxel mono-chemotherapy for metastatic breast cancer.

BACKGROUND: Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated. METHODS: Electronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy. RESULTS: Twenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38-66%, I2 = 98.97%), 58% (95% CI, 43-73%, I2 = 97.72%), 58% (95% CI, 48-68%, I2 = 97.17%), and 49% (95% CI, 41-56%, I2 = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35-45%, I2 = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59-73%, I2 = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89-8.40 months, I2 = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25-27.78 months, I2 = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered. CONCLUSIONS: The benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.

Proteomic characteristics and identification of PM2.5-induced differentially expressed proteins in hepatocytes and c-Myc silenced hepatocytes.

Proteomics and bioinformatics were applied to explore PM2.5-induced differentially expressed proteins (DEPs) in hepatocytes (L02 cells) and c-Myc-silenced hepatocytes. L02 cells and c-Myc-silenced hepatocytes were treated with PM2.5 for 24 h. Fifty-two DEPs were screened in L02 hepatocytes, of which 28 were upregulated and 24 were downregulated. Forty-one DEPs were screened in the c-Myc-silenced hepatocytes, of which 31 were upregulated and 10 were downregulated. GO analysis showed that DEPs in L02 cells were mainly concentrated in the cytosol and were involved in biological processes such as the response to metal ions. DEPs in c-Myc-silenced cells were mainly enriched in the extracellular space and were involved in lipoprotein metabolism. KEGG analysis showed that DEPs in L02 cells were mainly involved in arachidonic acid metabolism and mineral absorption. DEPs in c-Myc-silenced cells were mainly enriched in pathways involving nerve absorption, complement and coagulation cascades, and other pathways. Twenty key proteins, including Metallothionein-2A (MT2A), Metallothionein-1X (MT1X), zinc transporter ZIP10 (SLC39A10) and Serine protease 23 (PRSS23) were screened in two groups through analysis of protein-protein interactions. Based on the identification of the selected DEPs, PRSS23 and SLC39A10 might be the potential biomarker of PM2.5-induced carcinogenesis, which provide the scientific basis for further research into the carcinogenic mechanisms of PM2.5.

The predictive factors for postoperative hypoparathyroidism and its severity on the first postoperative day after papillary thyroid carcinoma surgery.

PURPOSE: The purpose of the study was to investigate the predictive factors for hypoparathyroidism and its severity on the first postoperative day (POD1) after total thyroidectomy (TT) with or without central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC). METHODS: From February 2014 to February 2019, 2550 PTC patients were admitted to our department. PTC patients who underwent TT were enrolled in this study. A parathyroid hormone (PTH) level lower than 15 pg/mL on POD1 was defined as hypoparathyroidism, and the severity of hypoparathyroidism was classified into three categories according to the level of PTH on POD1: mild hypoparathyroidism (10 pg/mL ≤ PTH < 15 pg/mL), moderate hypoparathyroidism (5 g/mL ≤ PTH < 10 pg/mL), and severe hypoparathyroidism (PTH < 5 pg/mL). Multiple clinical, pathological and surgical parameters of these two different groups were compared and analyzed to demonstrate the possible causes of hypoparathyroidism. Furthermore, patients who developed postoperative hypoparathyroidism were also included in a subgroup analysis according to the severity of their hypoparathyroidism. The underlying factors affecting different severities of hypoparathyroidism were also illustrated with univariate and multivariate analyses. RESULTS: Ultimately, 690 patients who underwent TT were enrolled in this retrospective study. Through the univariate analysis, different surgeons (P < 0.001), extent of CND (P = 0.009), prophylactic calcium supplementation (PCS) (P < 0.001), preoperative (pre-op) PTH level (P < 0.001), and pre-op phosphorus concentration (P = 0.022) were found to be significantly correlated with postoperative hypoparathyroidism. According to the multivariate analysis, PCS was the only independent high-risk factor for hypoparathyroidism. In the univariate analysis of patient subgroups with different severities of hypoparathyroidism, we demonstrated that the tumor T stage (P = 0.021) and pre-op PTH level (P < 0.001) were associated with the severity of hypoparathyroidism. Furthermore, after the multivariate analysis, hypertension (P < 0.001) and pre-op PTH (P < 0.001) were the two independent predictive factors for the severity of hypoparathyroidism after surgery. CONCLUSIONS: Postoperative PCS could increase the risk for PTC patients developing hypoparathyroidism after thyroid surgery. Patients with a history of hypertension and a relatively high pre-op PTH level may not develop severe hypoparathyroidism after TT with CND.

Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice.

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.

The pentatricopeptide repeat protein EMB1270 interacts with CFM2 to splice specific group II introns in Arabidopsis chloroplasts.

Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes. Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat (PPR) protein, is required for chloroplast biogenesis in Arabidopsis thaliana. Knockout of EMB1270 led to embryo arrest, whereas a mild knockdown mutant of EMB1270 displayed a virescent phenotype. Almost no photosynthetic proteins accumulated in the albino emb1270 knockout mutant. By contrast, in the emb1270 knockdown mutant, the levels of ClpP1 and photosystem I (PSI) subunits were significantly reduced, whereas the levels of photosystem II (PSII) subunits were normal. Furthermore, the splicing efficiencies of the clpP1.2, ycf3.1, ndhA, and ndhB plastid introns were dramatically reduced in both emb1270 mutants. RNA immunoprecipitation revealed that EMB1270 associated with these introns in vivo. In an RNA electrophoretic mobility shift assay (REMSA), a truncated EMB1270 protein containing the 11 N-terminal PPR motifs bound to the predicted sequences of the clpP1.2, ycf3.1, and ndhA introns. In addition, EMB1270 specifically interacted with CRM Family Member 2 (CFM2). Given that CFM2 is known to be required for splicing the same plastid RNAs, our results suggest that EMB1270 associates with CFM2 to facilitate the splicing of specific group II introns in Arabidopsis.

The histone deacetylase inhibitor tubacin mitigates endothelial dysfunction by up-regulating the expression of endothelial nitric oxide synthase.

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo We found that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found that these effects were not mediated by tubacin's inhibitory effect on HDAC6 activity, but rather were due to its ability to stabilize eNOS mRNA transcripts. Consistent with these findings, tubacin also inhibited proinflammatory cytokine-induced degradation of eNOS transcripts and impairment of endothelium-dependent relaxation in the mouse aorta. Furthermore, we found that tubacin-induced up-regulation in eNOS expression in vivo is associated with improved endothelial function in diabetic db/db mice and with a marked attenuation of ischemic brain injury in a murine stroke model. Our findings indicate that tubacin exhibits potent eNOS-inducing effects and suggest that this compound might be useful for the prevention or management of endothelial dysfunction-associated cardiovascular diseases.

Bioactive compounds induced in Physalis angulata L. by methyl-jasmonate: an investigation of compound accumulation patterns and biosynthesis-related candidate genes.

KEY MESSAGE: We employed both metabolomic and transcriptomic approaches to explore the accumulation patterns of physalins, flavonoids and chlorogenic acid in Physalis angulata and revealed the genes associated with the biosynthesis of bioactive compounds under methyl-jasmonate (MeJA) treatment. Physalis angulata L. is an annual Solanaceae plant with a number of medicinally active compounds. Despite the potential pharmacological benefits of P. angulata, the scarce genomic information regarding this plant has limited the studies on the mechanisms of bioactive compound biosynthesis. To facilitate the basic understanding of the main chemical constituent biosynthesis pathways, we performed both metabolomic and transcriptomic approaches to reveal the genes associated with the biosynthesis of bioactive compounds under methyl-jasmonate (MeJA) treatment. Untargeted metabolome analysis showed that most physalins, flavonoids and chlorogenic acid were significantly upregulated. Targeted HPLC-MS/MS analysis confirmed variations in the contents of two important representative steroid derivatives (physalins B and G), total flavonoids, neochlorogenic acid, and chlorogenic acid between MeJA-treated plants and controls. Transcript levels of a few steroid biosynthesis-, flavonoid biosynthesis-, and chlorogenic acid biosynthesis-related genes were upregulated, providing a potential explanation for MeJA-induced active ingredient synthesis in P. angulata. Systematic correlation analysis identified a number of novel candidate genes associated with bioactive compound biosynthesis. These results may help to elucidate the regulatory mechanism underlying MeJA-induced active compound accumulation and provide several valuable candidate genes for further functional study.

Soluble Epoxide Hydrolase Inhibition by t-TUCB Promotes Brown Adipogenesis and Reduces Serum Triglycerides in Diet-Induced Obesity.

Brown adipose tissue (BAT) is an important target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH) converts bioactive epoxy fatty acids (EpFAs) into less active diols. sEH inhibitors (sEHI) are beneficial in many chronic diseases by stabilizing EpFAs. However, roles of sEH and sEHI in brown adipogenesis and BAT activity in treating diet-induced obesity (DIO) have not been reported. sEH expression was studied in in vitro models of brown adipogenesis and the fat tissues of DIO mice. The effects of the sEHI, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy-benzoic acid (t-TUCB), were studied in vitro and in the obese mice via mini osmotic pump delivery. sEH expression was increased in brown adipogenesis and the BAT of the DIO mice. t-TUCB promoted brown adipogenesis in vitro. Although t-TCUB did not change body weight, fat pad weight, or glucose and insulin tolerance in the obese mice, it decreased serum triglycerides and increased protein expression of genes important for lipid metabolism in the BAT. Our results suggest that sEH may play a critical role in brown adipogenesis, and sEHI may be beneficial in improving BAT protein expression involved in lipid metabolism. Further studies using the sEHI combined with EpFA generating diets for obesity treatment and prevention are warranted.

Comparative metabolomic analysis reveals the variations in taxoids and flavonoids among three Taxus species.

BACKGROUND: Trees of the genus Taxus are highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel from Taxus trees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly among Taxus species. In our study, the metabolomes of three Taxus species have been investigated. RESULTS: A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated in T. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated in T. cuspidata and T. media. Our data suggested that there were higher-efficiency pathways to paclitaxel in T. cuspidata and T. media compared with in T. mairei. As an important class of active ingredients in Taxus trees, a majority of flavonoids were predominantly accumulated in T. mairei rather than T. media and T. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach. CONCLUSIONS: Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.

Tumor-associated macrophages correlate with phenomenon of epithelial-mesenchymal transition and contribute to poor prognosis in triple-negative breast cancer patients.

BACKGROUND: Tumor-associated macrophages (TAMs) are associated with poor outcomes in multiple solid cancers and play important roles in cancer progression. Epithelial-mesenchymal transition (EMT) may account for metastasis and recurrence. However, the association between TAMs and EMT is not clarified in triple-negative breast cancer (TNBC). The aim of this study was to investigate the effects of TAMs on EMT in TNBC. MATERIAL AND METHODS: We studied specimens from 278 patients with TNBC. TAMs marker cluster of differentiation 163 and EMT-related marker E-cadherin were detected by immunohistochemistry in TNBC tissues, and their clinical significance was evaluated from the patients' medical records. RESULTS: TNBC patients with polarized cluster of differentiation 163+ TAMs infiltration and low level of E-cadherin had a significantly higher risk of aggressive features, including recurrence, histologic differentiation, and lymph node metastasis. Infiltration of TAMs was also negatively correlated with E-cadherin in TNBC tissues. Multivariate analysis indicated that infiltration of TAMs and low expression of E-cadherin were independent prognostic factors of overall survival and disease-free survival in TNBC patients. CONCLUSIONS: High infiltration of TAMs was associated with low expression of E-cadherin and could be used as an unfavorable prognostic factor for patients with TNBC.

[Correlation of insulin-like growth factor 1 expression in placenta with DNA methylation and fetal macrosomia].

OBJECTIVE: To explore the correlation between methylation of insulin-like growth factor 1 (IGF-1) gene promoter and its placenta-specific expression and fetal macrosoma. METHODS: One hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF 1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. RESULTS: The expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter (r=0.128, P=0.295). IGF-1 promoter region in placenta showed a hypomethylation status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g (r=0.264, P=0.022). The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth. CONCLUSION: No linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetal growth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relatively normal range.

[Health risk assessment on pesticide residues in drinking water in Shenzhen].

OBJECTIVE: To conduct a health risk assessment of pesticide residues and its annual trend analysis in drinking water in Shenzhen City. METHODS: The water quality monitoring data of product water, pipe water and secondary supply water during from 2011 to 2013 were collected and analyzed. The risk evaluation models recommended by the U. S. Environmental Protection Agency (USEPA) were employed to perform health risk assessments for children and adults on the 12 non-carcinogenic materials (namely, heptachlor, pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, DDT, malathion, glyphosate, dimethoate, bentazone, atrazine, chlorothalonil, furadan). Results The results of the analysis for water quality from 84 factory samples, 11 peripheral samples and one secondary supply water sample showed that all of the measured indicators in the above mentioned water samples met the National Health Standards (GB 5749-2006) published by Ministry of Health of the People's Republic of China. The adults and children' s health indices (HIs) of the 12 non-carcinogenic materials were greater than 1 (2. 323 - 6. 312). Dimethoate in factory and peripheral water samples posed the largest risks of harm among the non-carcinogenic pollutants measured. And its HIi were also greater than 1 (1. 995 - 5. 094) and followed by hexachlorobenzene and heptachlor. Annual rising trend on health risk of the 12 pesticide residues indicated that their HIT on adults was 2323. 18 x 10(-3) in 2011, 2340. 18 x 10(-3) in 2012 and 2431. 97 x 10(-3) in 2013, and on children 2965. 07 x 10 (-3) in 2011, 2986. 77 x 10(-3) in 2012 and 3103. 93 x 10(-3) in 2013, respectively. This study also suggested that the average risk of peripheral water samples (HIT was equal to 2619. 64 x 10(-3) was greater than that of factory samples (HIT was same as 2366. 92 x 10(-3), and more children' s health risk than adults' risk. CONCLUSION: Health risks of pesticide residues in drinking water in Shenzhen have exceeded the threshold value and dimethoate was the main hazard and more children's health risk than adults' risk. Furthermore, there was an annual rising slowly trend on health risks of pesticide residues in drinking water.

Function characterization of a glyco-engineered anti-EGFR monoclonal antibody cetuximab in vitro.

AIM: To evaluate the biochemical features and activities of a glyco-engineered form of the anti-human epidermal growth factor receptor monoclonal antibody (EGFR mAb) cetuximab in vitro. METHODS: The genes encoding the Chinese hamster bisecting glycosylation enzyme (GnTIII) and anti-human EGFR mAb were cloned and coexpressed in CHO DG44 cells. The bisecting-glycosylated recombinant EGFR mAb (bisec-EGFR mAb) produced by these cells was characterized with regard to its glycan profile, antiproliferative activity, Fc receptor binding affinity and cell lysis capability. The content of galactose-α-1,3-galactose (α-Gal) in the bisec-EGFR mAb was measured using HPAEC-PAD. RESULTS: The bisec-EGFR mAb had a higher content of bisecting N-acetylglucosamine residues. Compared to the wild type EGFR mAb, the bisec-EGFR mAb exhibited 3-fold higher cell lysis capability in the antibody-dependent cellular cytotoxicity assay, and 1.36-fold higher antiproliferative activity against the human epidermoid carcinoma line A431. Furthermore, the bisec-EGFR mAb had a higher binding affinity for human FcγRIa and FcγRIIIa-158F than the wild type EGFR mAb. Moreover, α-Gal, which was responsible for cetuximab-induced hypersensitivity reactions, was not detected in the bisec-EGFR mAb. CONCLUSION: The glyco-engineered EGFR mAb with more bisecting modifications and lower α-Gal content than the approved therapeutic antibody Erbitux shows improved functionality in vitro, and requires in vivo validations.