Physical-Chemical Coupling Coassembly Approach to Branched Magnetic Mesoporous Nanochains with Adjustable Surface Roughness.

Self-assembly processes triggered by physical or chemical driving forces have been applied to fabricate hierarchical materials with subtle nanostructures. However, various physicochemical processes often interfere with each other, and their precise control has remained a great challenge. Here, in this paper, a rational synthesis of 1D magnetite-chain and mesoporous-silica-nanorod (Fe3O4&mSiO2) branched magnetic nanochains via a physical-chemical coupling coassembly approach is reported. Magnetic-field-induced assembly of magnetite Fe3O4 nanoparticles and isotropic/anisotropic assembly of mesoporous silica are coupled to obtain the delicate 1D branched magnetic mesoporous nanochains. The nanochains with a length of 2-3 µm in length are composed of aligned Fe3O4@mSiO2 nanospheres with a diameter of 150 nm and sticked-out 300 nm long mSiO2 branches. By properly coordinating the multiple assembly processes, the density and length of mSiO2 branches can well be adjusted. Because of the unique rough surface and length in correspondence to bacteria, the designed 1D Fe3O4&mSiO2 branched magnetic nanochains show strong bacterial adhesion and pressuring ability, performing bacterial inhibition over 60% at a low concentration (15 µg mL-1). This cooperative coassembly strategy deepens the understanding of the micro-nanoscale assembly process and lays a foundation for the preparation of the assembly with adjustable surface structures and the subsequent construction of complex multilevel structures.

Nucleation-Inhibited Emulsion Interfacial Assembled Polydopamine Microvesicles as Artificial Antigen-Presenting Cells.

Albeit microemulsion systems have emerged as efficient platforms for fabricating tunable nano/microstructures, lack of understanding on the emulsion-interfacial assembly hindered the control of fabrication. Herein, a nucleation-inhibited microemulsion interfacial assembly method is proposed, which deviates from conventional interfacial nucleation approaches, for the synthesis of polydopamine microvesicles (PDA MVs). These PDA MVs exhibit an approximate diameter of 1 µm, showcasing a pliable structure reminiscent of cellular morphology. Through modifications of antibodies on the surface of PDA MVs, their capacity as artificial antigen presentation cells is evaluated. In comparison to solid nanoparticles, PDA MVs with cell-like structures show enhanced T-cell activation, resulting in a 1.5-fold increase in CD25 expression after 1 day and a threefold surge in PD-1 positivity after 7 days. In summary, the research elucidates the influence of nucleation and interfacial assembly in microemulsion polymerization systems, providing a direct synthesis method for MVs and substantiating their effectiveness as artificial antigen-presenting cells.

HMGA1 regulates the mitochondrial apoptosis pathway in sepsis-induced cardiomyopathy.

High mobility group protein AT-hook 1 (HMGA1), an architectural transcription factor, has previously been reportedto play an essential role in architectural remodeling processes. However, its effects on cardiovascular diseases, particularly sepsis-induced cardiomyopathy, have remained unclear. The study aimed to investigate the role of HMGA1 in lipopolysaccharide-induced cardiomyopathy. Mice subjected to lipopolysaccharide for 12 h resulted in cardiac dysfunction. We used an adeno-associated virus 9 delivery system to achieve cardiac-specific expression of the HMGA1 gene in the mice. H9c2 cardiomyocytes were infected with Ad-HMGA1 to overexpress HMGA1 or transfected with si-HMGA1 to knock down HMGA1. Echocardiography was applied to measure cardiac function. RT-PCR was used to detect the transcriptional level of inflammatory cytokines. CD45 and CD68 immunohistochemical staining were used to detect inflammatory cell infiltration and TUNEL staining to evaluate the cardiomyocyte apoptosis, MitoSox was used to detect mitochondrial reactive oxygen species, JC-1 was used todetect Mitochondrial membrane potential. Our findings revealed that the overexpression of HMGA1 exacerbated myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Additionally, we also observed that H9c2 cardiomyocytes with HMGA1 overexpression exhibited enhanced inflammation and apoptosis upon stimulation with lipopolysaccharide for 12 h. Conversely, HMGA1 knockdown in H9c2 cardiomyocytes attenuated lipopolysaccharide-induced cardiomyocyte inflammation and apoptosis. Further investigations into the molecular mechanisms underlying these effects showed that HMGA1 promoted lipopolysaccharide-induced mitochondrial-dependent cardiomyocyte apoptosis. The study reveals that HMGA1 worsens myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Mechanically, HMGA1 exerts its effects by regulating the mitochondria-dependent apoptotic pathway.

ATX1 and HUB1/2 promote recruitment of the transcription elongation factor VIP2 to modulate the floral transition in Arabidopsis.

Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase-associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1-2 hub1-10 hub2-2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1-10 hub2-2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1-10 hub2-2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1-10 hub2-2 and FRI atx1-2 plants resulted in early flowering like that observed in FRI vip2-10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.

Rapid and sensitive quantitation of amitraz in orange, tomato, and eggplant samples using immunochromatographic assay.

Amitraz (AMT) is a broad-spectrum formamidine insecticide and acaricide. In this study, we produced an anti-AMT monoclonal antibody (mAb) with high performance. The half-maximal inhibitory concentration of the anti-AMT mAb was 4.418 ng/mL, the cross reactivity with other insecticides was negligible, and an affinity constant was 2.06 × 109 mmol/L. Additionally, we developed an immunochromatographic assay for the rapid detection of AMT residues in oranges, tomatoes, and eggplants. The cut-off values were 2000 µg/kg in oranges and tomato samples and 1000 µg/kg in eggplant samples and the calculated limits of detection were 14.521 µg/kg, 6.281 µg/kg, and 3.518 µg/kg in oranges, tomatoes, and eggplants, respectively, meeting the detection requirements for AMT in fruits and vegetables. The recovery rates ranged between 95.8 % and 105.2 %, consistent with the recovery rates obtained via LC-MS/MS. Our developed immunochromatographic assay can effectively, accurately, and rapidly determine AMT residues in oranges, tomatoes, and eggplants.

Clinical comparative analysis of 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques in treating type B aortic dissections with inadequate proximal landing zones.

BACKGROUND: This study aims to compare the clinical effects of two distinct surgical approaches, namely 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques, in treating patients with Stanford type B aortic dissections (TBAD) characterized by inadequate proximal landing zones. METHODS: A retrospective analysis was conducted on 84 patients with type B aortic dissection (TBAD) who underwent thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) reconstruction at our center from January 2022 to July 2023. Based on the different surgical approaches, the patients were divided into two groups: the group assisted by 3D printing for extracorporeal pre-fenestration (n = 44) and the group using the castor integrated branch stent (n = 40). Clinical indicators: including general patient information, operative time, surgical success rate, intraoperative and postoperative complication rates, re-intervention rate, and mortality, as well as postoperative aortic remodeling, were compared between the two groups. The endpoint of this study is the post-TEVAR mortality rate in patients. RESULTS: The surgical success rate and device deployment success rate were 100% in both groups, with no statistically significant difference (P > 0.05). However, the group assisted by 3D printing for extracorporeal pre-fenestration had a significantly longer operative time (184.20 ± 54.857 min) compared to the group using the castor integrated branch stent (152.75 ± 33.068 min), with a statistically significant difference (t = 3.215, p = 0.002, P < 0.05). Moreover, the incidence of postoperative cerebral infarction and beak sign was significantly lower in the group assisted by 3D printing for extracorporeal pre-fenestration compared to the castor-integrated branch stent group, demonstrating statistical significance. There were no significant differences between the two groups in terms of other postoperative complication rates and aortic remodeling (P > 0.05). Notably, computed tomography angiography images revealed the expansion of the vascular true lumen and the reduction of the false lumen at three specified levels of the thoracic aorta. The follow-up duration did not show any statistically significant difference between the two groups (10.59 ± 4.52 vs. 9.08 ± 4.35 months, t = 1.561, p = 0.122 > 0.05). Throughout the follow-up period, neither group experienced new endoleaks, spinal cord injuries, nor limb ischemia. In the castor-integrated branch stent group, one patient developed a new distal dissection, prompting further follow-up. Additionally, there was one case of mortality due to COVID-19 in each group. There were no statistically significant differences between the two groups in terms of re-intervention rate and survival rate (P > 0.05). CONCLUSION: Both 3D printing-assisted extracorporeal pre-fenestration TEVAR and castor-integrated branch stent techniques demonstrate good safety and efficacy in treating Stanford type B aortic dissection with inadequate proximal anchoring. The 3D printing-assisted extracorporeal pre-fenestration TEVAR technique has a lower incidence of postoperative cerebral infarction and beak sign, while the castor-integrated branch stent technique has advantages in operative time.

Predictive value of cytokines combined with human neutrophil lipocalinin acute ischemic stroke-associated pneumonia.

OBJECTIVE: To explore the predictive value of interleukin-6 (IL-6) combined with human neutrophil lipocalin (HNL) of stroke-associated pneumonia (SAP) in patients who were diagnosed with acute ischemic stroke (AIS). METHODS: 108patients were divided into two groups: pneumonia group (52 cases) and non-pneumonia group (56 cases), according to whether the patients developed SAP within 7 days of admission. General information was compared between the two groups, like age, gender, history of hypertension, diabetes mellitus, cardiovascular disease, dysphagia, smoking and alcoholhistory. Clinical data were recorded and compared, including lipid profile, interleukin-6 (IL-6), homocysteine (Hcy), National Institutes of Health Stroke Scale (NIHSS) score, and HNL. Multivariate Logistic regression analysis was used to screen the risk factors of AIS-AP, and the predictive value of IL-6 and HNL alone and in combination was evaluated by receiver operating characteristic curve (ROC curve). RESULTS: Logistic regression analysis showed that dysphagia (OR,0.018; 95% CI, 0.001 ~ 0.427; P = 0.013), increased NIHSS scores(OR,0.012; 95% CI, 0.000 ~ 0.434; P = 0.016), and high levels of IL-6 (OR,0.014; 95% CI, 0.000 ~ 0.695; P = 0.032)and HNL (OR,0.006; 95% CI, 0.000 ~ 0.280; P = 0.009) were independent risk factors for SAP with significant difference (all P < 0.05). According to the ROC curve analysis of IL-6, the area under the curve (AUC) was 0.881 (95% CI: 0.820 ~ 0.942), and the optimal cutoff value was 6.89 pg/mL with the sensitivity of 73.1% and specificity of 85.7%. As for the ROC curve analysis of HNL, the AUC was 0.896 (95% CI: 0.839 ~ 0.954), and the best cutoff value was 99.66ng/mL with the sensitivity of 76.9% and specificity of 89.3%. The AUC of the combination of IL-6 and HNL increased to 0.952 (95% CI: 0.914 ~ 0.989), and the sensitivity and specificity increased to 80.8% and 92.9%, respectively. CONCLUSION: In this research, the levels of IL-6 ≥ 6.89 pg/mL and HNL ≥ 99.66ng/mL were considered as risk factors for AIS patients complicated with SAP. The combined detection had higher predictive value for patients with SAP, which may help to identify who were in highrisk.

Periselectivity and ambimodal transition states in cycloadditions of tetrachloro-o-benzoquinone with 6,6-dimethylfulvene.

The reaction mechanism of cycloadditions of tetrachloro-o-benzoquinone with 6,6-dimethylfulvene were systematically investigated with density functional theory calculations. It was found that conditional primary interactions stabilize the ambimodal transition states in the endo pathways. Ambimodal transition states lead to [6 + 4]/[4 + 2] adducts or [4 + 2]/[2 + 4] adducts, which interconvert through 3,3-sigmatropic shift reactions. The substituent effects on periselectivity were also investigated.

Computational Determination of the Mechanism of the Palladium-Catalyzed Domino Reaction of ortho-Iodostyrene, Oxanorbornadiene, and Phenylboronic Acid.

The palladium-catalyzed three-component domino reaction of ortho-iodostyrene, 2,3-dicarbomethoxy-7-oxanorbornadiene (ONBD), and phenylboronic acid discovered by the Lautens group provides a convenient method to synthesize indenes derivatives. Herein, density functional theory (DFT) calculations were employed to explore the detailed mechanism of this domino reaction. The computational results suggest that the alkene-insertion-first and the transmetalation-first mechanisms are competitive, and the former mechanism is slightly more favorable because of the difficult intramolecular alkene insertion of the alkyl-PdII-aryl than alkyl-PdII-I complex. Further analysis on substituents of ONBD unveils the impacts of noncovalent interactions and electronic effect on the rate-determining retro-Diels-Alder process. The understanding of this domino reaction has important implications for developing a novel palladium-catalyzed domino reaction with a retro-Diels-Alder strategy.

3D Printing-Assisted versus Conventional Extracorporeal Fenestration Tevar for Stanford Type B Arteries Dissection with Undesirable Proximal Anchoring Zone: Efficacy Analysis.

BACKGROUND: To compare the outcomes of two Thoracic Endovascular Aortic Repair (TEVAR) techniques of Left Subclavian Artery (LSA) reconstruction for Stanford Type B Aortic Dissection (TBAD) patients with undesirable proximal anchoring zone. METHODS: We retrospectively reviewed 57 patients with TBAD who underwent either three dimensional (3D)-printing-assisted extracorporeal fenestration (n = 32) or conventional extracorporeal fenestration (n = 25) from December 2021 to January 2023. We compared their demographic characteristics, operative time, technical success rate, complication rate, secondary intervention rate, mortality rate, and aortic remodeling. RESULTS: Compared with the conventional group, the 3D-printing-assisted group had a significantly shorter operative time (147.84 ± 33.94 min vs. 223.40 ± 65.93 min, p < 0.001), a significantly lower rate of immediate endoleak (3.1% vs. 24%, p = 0.048) and a significantly higher rate of true lumen diameter expansion in the stent-graft segment (all p < 0.05), but a significantly longer stent graft modification time (37.63 ± 2.99 min vs. 28.4 ± 2.12 min, p < 0.001). There were no significant differences in other outcomes between the two groups (p > 0.05). The degree of false lumen thrombosis was higher in the stent-graft segment than in the non-stent-graft segment in both groups and the difference was statistically significant (X2 = 5.390, 4.878; p = 0.02, 0.027). CONCLUSIONS: Both techniques are safe and effective for TBAD with an undesirable proximal landing zone. The 3D-printing-assisted extracorporeal fenestration TEVAR technique has advantages in operative time, endoleak risk, and aortic remodeling, while the traditional extracorporeal fenestration TEVAR technique has advantages in stent modification.

circFAM134B is a key factor regulating reticulophagy-mediated ferroptosis in hepatocellular carcinoma.

Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B (FAM134B), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and western blot (WB) assays in HCC cells. RNA pull-down and mass spectrometry analyses suggested that circFAM134B and FAM134B mRNA were enriched with several common interacting proteins. Among them, poly (A) binding protein cytoplasmic 4 (PABPC4) was identified as the most enriched binding partner. It was proven to be a novel antagonist against the nonsense-mediated mRNA decay (NMD) mechanism. We then applied RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and NMD reporter gene assays to further explore the exact role and underlying mechanism of circFAM134B-PABPC4-FAM134B axis in HCC cells. circFAM134B was confirmed as a sponge that competitively interacted with PABPC4, thereby influencing FAM134B mRNA nonsense decay. Our results provide novel evidences and strategies for the comprehensive treatment of HCC.

Nanoparticles with transformable physicochemical properties for overcoming biological barriers.

In recent years, tremendous progress has been made in the development of nanomedicines for advanced therapeutics, yet their unsatisfactory targeting ability hinders the further application of nanomedicines. Nanomaterials undergo a series of processes, from intravenous injection to precise delivery at target sites. Each process faces different or even contradictory requirements for nanoparticles to pass through biological barriers. To overcome biological barriers, researchers have been developing nanomedicines with transformable physicochemical properties in recent years. Physicochemical transformability enables nanomedicines to responsively switch their physicochemical properties, including size, shape, surface charge, etc., thus enabling them to cross a series of biological barriers and achieve maximum delivery efficiency. In this review, we summarize recent developments in nanomedicines with transformable physicochemical properties. First, the biological dilemmas faced by nanomedicines are analyzed. Furthermore, the design and synthesis of nanomaterials with transformable physicochemical properties in terms of size, charge, and shape are summarized. Other switchable physicochemical parameters such as mobility, roughness and mechanical properties, which have been sought after most recently, are also discussed. Finally, the prospects and challenges for nanomedicines with transformable physicochemical properties are highlighted.

Research on quality evaluation of innovation and entrepreneurship education for college students based on random forest algorithm and logistic regression model.

The quality evaluation of innovation and entrepreneurship (I&E) in the education sector is achieving worldwide attention as empowering nations with high quality talents is quintessential for economic progress. China, a pioneer in the world market in almost all sectors have transformed its educational policies and incorporated entrepreneurial skills as a part of their education models to further catalyst the country's economic progress. This research focuses on building a novel hybrid Machine Learning (ML) model by integrating two powerful algorithms namely Random Forest (RF) and Logistic Regression (LR) to assess the intensity of the I&E in education from the data acquired from 25 leading Higher Educational Institution's (HEI) in different provinces. The major contributions to the work are, (1) construction of quality index for each topic of interest using individual RF, (2) ranking the indicators based on the quality index to assess the strength and weaknesses, (3) and finally use the LR algorithm study the quality of each indicator. The efficacy of the proposed hybrid model is validated using the benchmark classification metrics to assess its learning and prediction performance in evaluating the quality of I&E education. The result of the research portrays that the universities have now started to integrate entrepreneurship skills as a part of the curriculum, which is evident from the better ranking of the topic curriculum development which is followed by the enrichment of skills. This comprehensive research will help the institutions to identify the potential areas of growth to boost the economic development and improve the skill set necessary for I&E education among college students.

Computational Elucidation on the Conformational Control of Selectivity in Intramolecular Ring-Closing Metathesis vs Intermolecular Homometathesis.

The ring-closing metathesis reaction of diene plays an important role in the construction of cyclic compounds. In this research, density functional theory (DFT) calculations were conducted to elucidate the mechanisms and origins of the selectivity of ring-closing metathesis and homometathesis. The computational results suggest that the selectivity is determined by the substrate conformation. For the ester-tethered substrate, the homometathesis is more favorable, due to the planar structure of ester facilitating the conjugative effect of the formed E-homometathesis product. For the amide-tethered substrate, the ring-closing metathesis product is the only observed product because the steric hindrance of N-substituents disfavors homometathesis.

Rapid and sensitive detection of chlordimeform in cucumber and tomato samples using an immunochromatographic assay.

Chlordimeform (CDM) is a broad-spectrum and highly effective insecticide and acaricide used to control pests in agriculture. We produced two monoclonal antibodies (mAbs) against CDM and developed an immunochromatographic assay to screen CDM in cucumbers and tomatoes. MAb 4A3 had high sensitivity with a 50% inhibitory concentration of 0.287 ng mL-1. The assay had a cut-off value of 25 µg kg-1 and a visual limit of detection (vLOD) of 1 µg kg-1 in cucumbers and a cut off value of 50 µg kg-1 and a vLOD of 2.5 µg kg-1 in tomatoes. The calculated limit of detection (cLOD) in cucumbers and tomatoes was 0.115 µg kg-1 and 0.215 µg kg-1, respectively. The recovery rates were 97.9% to 106.9% for cucumbers and 97.8% to 107.4% for tomatoes, consistent with the results obtained from indirect competitive ELISA. Our findings showed that the immunochromatographic assay is an efficient and accurate method for CDM detection in cucumbers and tomatoes.

Elemental composition and microbial community differences between wastewater treatment plant effluent and local natural surface water: A Zhengzhou city study.

Wastewater treatment plant (WWTP) effluent is discharged into rivers as supplemental water, which may result in ecological risk. This study compares the element composition and microbial community of WWTP effluent and natural surface water (NSW) and reveals the potential ecological risk of WWTP effluent discharge. Twenty recently upgraded WWTPs and three relatively large reservoirs in Zhengzhou city, China, were selected. The contents of N, P, S, K, Ca, Mg, B, Si, Na, Fe, Mn, Co, Ni and Sn were significantly higher in WWTP effluent than in NSW, while those of Mo, V, Pb and Cd were significantly lower. There was no significant difference between WWTP effluent and NSW in terms of the element imbalance index (IMI) (representing the extent of imbalance of element proportions) relative to the class IV surface water quality standard (the control standard for most Chinese rivers). The macronutrient IMI relative to the Hoagland formula was significantly lower in WWTP effluent than in NSW, and WWTP effluent discharge could significantly lower this index in NSW; this may be an important cause of primary productivity explosion. The microbial diversity was significantly higher in WWTP effluent than in NSW. The predicted relative abundances of mobile genetic elements and oxidative-stress-tolerant phenotypes were significantly higher in WWTP effluent than in NSW, whereas the abundance of gram-negative phenotypes was significantly lower, and that of potential pathogenic phenotypes was slightly lower. The effluent from upgraded WWTPs exhibited a low risk of pathogen diffusion but a high risk of antibiotic resistance gene diffusion. The element composition and microbial community should be considered when evaluating the ecological risk of WWTP effluent discharge.

Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.

Impacts of a bacterial algicide on metabolic pathways in Chlorella vulgaris.

Chlorella is a dominant species during harmful algal blooms (HABs) worldwide, which bring about great environmental problems and are also a serious threat to drinking water safety. Application of bacterial algicides is a promising way to control HABs. However, the identified bacterial algicides against Chlorella and the understanding of their effects on algal metabolism are very limited. Here, we isolated a novel bacterium Microbacterium paraoxydans strain M1 that has significant algicidal activities against Chlorella vulgaris (algicidal rate 64.38 %, at 120 h). Atrazine-desethyl (AD) was then identified from strain M1 as an effective bacterial algicide, with inhibition or algae-lysing concentration values (EC50) of 1.64 µg/mL and 1.38 µg/mL, at 72 h and 120 h, respectively. LAD (2 µg/mL AD) or HAD (20 µg/mL AD) causes morphology alteration and ultrastructure damage, chlorophyll a reduction, gene expression regulation (for example, psbA, 0.05 fold at 24 h, 2.97 fold at 72 h, and 0.23 fold of the control in HAD), oxidative stress, lipid oxidation (MDA, 2.09 and 3.08 fold of the control in LAD and HAD, respectively, at 120 h) and DNA damage (average percentage of tail DNA 6.23 % at 120 h in HAD, slight damage: 5∼20 %) in the algal cells. The impacts of AD on algal metabolites and metabolic pathways, as well as the algal response to the adverse effects were investigated. The results revealed that amino acids, amines, glycosides and urea decreased significantly compared to the control after 24 h exposure to AD (p < 0.05). The main up-regulated metabolic pathways implied metabonomic resistance and defense against osmotic pressure, oxidative stress, photosynthesis inhibition or partial cellular structure damage, such as phenylalanine metabolism, arginine biosynthesis. The down-regulated glycine, serine and threonine metabolism is a major lead in the algicidal mechanism according to the value of pathway impact. The down-regulated glycine, and serine are responsible for the downregulation of glyoxylate and dicarboxylate metabolism, aminoacyl-tRNA biosynthesis, glutathione metabolism, and sulfur metabolism, which strengthen the algae-lysing effect. It is the first time to highlight the pivotal role of glycine, serine and threonine metabolism in algicidal activities, which provided a new perspective for understanding the mechanism of bacterial algicides exerting on algal cells at the metabolic level.

Clinicopathological and prognostic significance of COX-2 in glioma patients: a meta-analysis.

BACKGROUND: In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. OBJECTIVE: To evaluate the correlation of COX-2 with the prognosis in glioma patients. METHODS: Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. RESULTS: In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. CONCLUSION: The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

INTRODUçãO: Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. OBJETIVO: Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. MéTODOS: Estudos elegíveis sobre este assunto foram incluídos e foram estimados odds ratios (ORs) e hazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. RESULTADOS: No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57­2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69­3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. CONCLUSãO: O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.

Clinicopathological and prognostic significance of COX-2 in glioma patients: a meta-analysis / Significância clinicopatológica e prognóstica da COX-2 em pacientes com glioma: uma metanálise

Abstract Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients. Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

Resumo Introdução Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. Objetivo Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. Métodos Estudos elegíveis sobre este assunto foram incluídos e foram estimadosodds ratios (ORs) ehazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. Resultados No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57-2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69-3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. Conclusão O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.