[Role of Ferroptosis in Non-small Cell Lung Cancer and Progress 
of Traditional Chinese Medicine Intervention].

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with high morbidity and mortality worldwide. Ferroptosis is a new type of programmed cell death caused by abnormal accumulation of iron-dependent reactive oxygen species (ROS) leading to lipid peroxidation. It involves the balance between iron metabolism, lipid metabolism, oxygen free radical reaction and lipid peroxidation. Recent studies have found that ferroptosis is closely related to the occurrence and development of NSCLC. Due to the emergence of chemotherapy resistance and radiotherapy resistance in the treatment of NSCLC, there is an urgent need to develop new effective drugs and treatment strategies. Traditional Chinese medicine has unique advantages in the prevention and treatment of NSCLC due to its multi-targets and minimal side effects. In this review, we summarize the mechanism of ferroptosis in NSCLC, and discuss the research status of active ingredients of traditional Chinese medicine, single-herb traditional Chinese medicine and Chinese herbal compounds in the intervention of NSCLC through ferroptosis, in order to provide a new theoretical basis for the research of ferroptosis pathway and the prevention and treatment of NSCLC by targeted ferroptosis of traditional Chinese medicine.
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Modifying the Molecular Structure of Carbon Nanotubes through Gas-Phase Reactants.

Current approaches to carbon nanotube (CNT) synthesis are limited in their ability to control the placement of atoms on the surface of nanotubes. Some of this limitation stems from a lack of understanding of the chemical bond-building mechanisms at play in CNT growth. Here, we provide experimental evidence that supports an alkyne polymerization pathway in which short-chained alkynes directly incorporate into the CNT lattice during growth, partially retaining their side groups and influencing CNT morphology. Using acetylene, methyl acetylene, and vinyl acetylene as feedstock gases, unique morphological differences were observed. Interwall spacing, a highly conserved value in natural graphitic materials, varied to accommodate side groups, increasing systematically from acetylene to methyl acetylene to vinyl acetylene. Furthermore, attenuated total reflectance Fourier-transfer infrared spectroscopy (ATR-FTIR) illustrated the existence of intact methyl groups in the multiwalled CNTs derived from methyl acetylene. Finally, the nanoscale alignment of the CNTs grown in vertically aligned forests differed systematically. Methyl acetylene induced the most tortuous growth while CNTs from acetylene and vinyl-acetylene were more aligned, presumably due to the presence of polymerizable unsaturated bonds in the structure. These results demonstrate that feedstock hydrocarbons can alter the atomic-scale structure of CNTs, which in turn can affect properties on larger scales. This information could be leveraged to create more chemically and structurally complex CNT structures, enable more sustainable chemical pathways by avoiding the need for solvents and postreaction modifications, and potentially unlock experimental routes to a host of higher-order carbonaceous nanomaterials.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Melatonin enhances stem strength by increasing lignin content and secondary cell wall thickness in herbaceous peony.

Cut flower quality is severely restrained by stem bending due to low stem strength. Melatonin has been shown to function in many aspects of plant growth and development, yet whether it can enhance stem strength, and the corresponding underlying mechanisms remain unclear. We investigated the role of melatonin in enhancement of stem strength in herbaceous peony (Paeonia lactiflora Pall.) by applying exogenous melatonin and changing endogenous melatonin biosynthesis. Endogenous melatonin content positively correlated with lignin content and stem strength in various P. lactiflora cultivars. Supplementation with exogenous melatonin significantly enhanced stem strength by increasing lignin content and the S/G lignin compositional ratio, up-regulating lignin biosynthetic gene expression. Moreover, overexpression of TRYPTOPHAN DECARBOXYLASE GENE (TDC) responsible for the first committed step of melatonin biosynthesis in tobacco, significantly increased endogenous melatonin, which further increased the S/G ratio and stem strength. In contrast, silencing PlTDC in P. lactiflora decreased endogenous melatonin, the S/G ratio and stem strength. Finally, manipulating the expression of CAFFEIC ACID O-METHYLTRANSFERASE GENE (COMT1), which is involved in both melatonin and lignin biosynthesis, showed even greater effects on melatonin, the S/G ratio and stem strength. Our results suggest that melatonin has a positive regulatory effect on P. lactiflora stem strength.

Conversion of failed proximal femoral nail antirotation to uncemented or cemented femoral component fixation: a multicentre retrospective study with a median 10-year follow-up.

BACKGROUND: Conversion of a failed proximal femoral nail antirotation (PFNA) to a total hip arthroplasty (THA) is becoming increasingly universal. However, consensus has not been reached regarding which device (uncemented or hybrid THA) to use. The aim of this retrospective study was to compare the clinical outcomes of the conversion of failed PFNAs to uncemented versus hybrid THAs in the elderly population. METHODS: Consecutive elderly patients with prior failed PFNAs treated with uncemented or hybrid THA from January 2008 to December 2019 were retrospectively identified from two medical centres. The primary outcome was implant survival after THA revision; secondary outcomes were the functional outcomes assessed using the Harris Hip Score (HHS) and the incidence of key THA-related complications. RESULTS: A total of 236 patients (uncemented THA, n = 116; hybrid THA, n = 120) were eligible for this study. Kaplan-Meier survival curves demonstrated that the 10-year cumulative survival rates were 0.801 (95% confidence interval [CI], 0.783-0.852) in the uncemented THA group versus 0.925 (95% CI, 0.861-0.964) in the hybrid THA group (hazard ratio [HR] 0.36 [95% CI 0.24-0.56], p = 0.004). From the 72nd month after the revision to the last follow-up, functional outcomes differed considerably between cohorts (each p < 0.05), and the rate of key THA-related complications was comparable between cohorts (p = 0.004). CONCLUSION: For elderly patients with prior failed PFNAs who experienced uncemented or hybrid THA, hybrid THA revision may provide a clinically significant improvement over uncemented THA revision with regard to implant survival, functional outcomes, and THA-related complications compared to uncemented THA revision.

Transarterial Chemoembolization Combined With Lenvatinib Plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study.

Purpose: To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined. Results: A total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699). Conclusion: TACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.

Circ_0001667 knockdown blocks cancer progression and attenuates adriamycin resistance by depleting NCOA3 via releasing miR-4458 in breast cancer.

Accumulating evidence suggests that developmental chemoresistance in cancers is closely associated with the dysregulation of circular RNA transcriptions. The objective of this study is to disclose the role of circ_0001667 and provide a potential functional mechanism in breast cancer. Quantitative real-time PCR was applied for the analysis of circ_0001667, microRNA-4458 (miR-4458) and nuclear receptor coactivator 3 (NCOA3) expression. In adriamycin (ADM)-resistant cell lines, we investigated cell proliferation using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and colony formation assay. Cell migration and cell invasion were determined by transwell assay. The protein levels of multi-drug resistance-1, matrix metalloproteinases-9, cleaved-caspase3, cleaved-caspase9 and NCOA3 were detected by western blot. ADM resistance was ascertained by IC50 value using MTT assay. Cell apoptosis was checked by flow cytometry assay. The putative relationship between miR-4458 and circ_0001667 and NCOA3 was validated by pull-down assay, dual-luciferase reporter assay or RNA Immunoprecipitation assay. Circ_0001667 knockdown inhibited MCF-7/ADM and MDA-MB-231/ADM cell proliferation, migration, invasion and ADM resistance. MiR-4458 was a target of circ_0001667, and its expression was decreased in ADM-resistant tumor tissues and cells. MiR-4458 inhibition reversed the effects of circ_0001667 knockdown. In depth, NCOA3 was a target of circ_0001667, and circ_0001667 knockdown weakened NCOA3 expression by releasing miR-4458. MCF-7/ADM and MDA-MB-231/ADM cell proliferation, migration, invasion, and ADM resistance inhibited by miR-4458 restoration were recovered by NCOA3 overexpression. Circ_0001667 knockdown also repressed tumor growth and ADM resistance in vivo. Circ_0001667 knockdown blocks cancer progression and attenuates ADM resistance by depleting NCOA3 via releasing miR-4458 in breast cancer.

Silicon enhances stem strength by promoting lignin accumulation in herbaceous peony (Paeonia lactiflora Pall.).

Herbaceous peony (Paeonia lactiflora Pall.) is a popular high-end cut flower, but stem bending caused by low stem strength severely decreases its quality. To enhance stem strength, the regulatory effects of exogenous silicon were investigated in P. lactiflora. The results showed that silicon application enhanced stem strength by increasing the thickness of secondary cell walls and the layers of thickened secondary cells. Moreover, more lignin accumulated, particularly G-lignin and S-lignin, and the activities of lignin biosynthetic enzymes increased with silicon application. In addition, based on transcriptome analysis, silicon application induced the expression of genes participating in lignin biosynthesis pathway. Among them, hydroxycinnamoyl-CoA: shikimate hydroxycinnamoyl transferase gene (HCT1) was isolated from P. lactiflora and found to be mainly localized in the cytoplasm of cells. Overexpression of PlHCT1 increased the layers of thickened secondary cells and lignin accumulation in tobacco, resulting in enhanced stem strength and demonstrably straight stems. Finally, silicon content, lignin content and PlHCT1 expression in P. lactiflora cultivars with high stem strengths were totally higher than those in cultivars with low stem strengths. These results indicated that silicon application enhanced stem strength by promoting lignin accumulation in P. lactiflora, which has prospects for stem quality improvement in general.

A Paeonia ostii caffeoyl-CoA O-methyltransferase confers drought stress tolerance by promoting lignin synthesis and ROS scavenging.

Paeonia ostii is an emerging woody oil crop, but drought severely inhibits its growth and promotion in arid or semiarid areas, and little is known about the mechanism governing this inhibition. In this study, the full-length cDNA of a caffeoyl-CoA O-methyltransferase gene (CCoAOMT) from P. ostii was isolated, and determined to be comprised of 987 bp. PoCCoAOMT encoded a 247-amino acid protein, which was located in the nucleus and cytosol. Significantly higher PoCCoAOMT transcription was detected in P. ostii treated with drought stress. Subsequently, the constitutive overexpression of PoCCoAOMT in tobacco significantly conferred drought stress tolerance. Under drought stress, transgenic lines exhibited lower reactive oxygen species (ROS) accumulation, and higher antioxidant enzyme activities and photosynthesis. Moreover, the expression levels of senescence-associated genes were significantly downregulated, whereas the expression levels of lignin biosynthetic genes and PoCCoAOMT were significantly upregulated in transgenic lines. Similarly, transgenic lines produced significantly higher lignin, especially guaiacyl-lignin. These results suggest that PoCCoAOMT is a vital gene in promoting lignin synthesis and ROS scavenging to confer drought stress tolerance in P. ostii.

The mechanism of and the association between interleukin-27 and chemotherapeutic drug sensitivity in lung cancer.

Interleukins (ILs) are involved in the occurrence and development of numerous types of cancer, and serve a critical role in the development of effective cancer therapeutics. The aim of the present study was to investigate the effect of IL-27 on chemotherapy resistance in lung cancer cells, and analyze its potential molecular mechanism in lung cancer tissues. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were performed to examine the RNA and protein expression levels of IL-27. A Cell Counting Kit-8 assay was performed to evaluate the proliferation rates of the lung cancer line A549. Flow cytometry was subsequently applied to determine the rate of apoptosis in A549 cells. The data obtained revealed that the expression of IL-27 with cisplatin, significantly suppressed the proliferation and apoptosis of A549 cells compared with that in the cisplatin treatment group alone. The expression of Akt and apoptosis factors such as Caspase-3 and Bcl-2/Bax also ascertained that upregulated IL-27 inhibited the development of cancer and increased apoptosis in the A549 cells. Therefore, IL-27 may represent a potential target for antitumor therapy, especially when considering the clinical challenges presented by the development of chemoresistance in tumors. These findings suggest that IL-27 is a promising biomarker and represents a novel treatment strategy for patients with lung cancer.

Coordinated Actions Between p97 and Cullin-RING Ubiquitin Ligases for Protein Degradation.

The cullin-RING ubiquitin ligases comprise the largest subfamily of ubiquitin ligases. They control ubiquitylation and degradation of a large number of protein substrates in eukaryotes. p97 is an ATPase domain-containing protein segregase. It plays essential roles in post-ubiquitylational events in the ubiquitin-proteasome pathway. Together with its cofactors, p97 collaborates with ubiquitin ligases to extract ubiquitylated substrates and deliver them to the proteasome for proteolysis. Here we review the structure, functions, and mechanisms of p97 in cellular protein degradation in coordination with its cofactors and the cullin-RING ubiquitin ligases.

An Antisense Oligonucleotide Drug Targeting miR-21 Induces H1650 Apoptosis and Caspase Activation.

Non-small cell lung cancer is the most common malignant tumor in the world. Currently, chemotherapy is still the major method for non-small cell lung cancer treatment, but the problem of cancer drug resistance still exists, so we designed 5 different phosphorothioate oligonucleotides to silence key genes in tumor cell development, which could help avoid inducing cancer cell drug resistance. MicroRNAs have been shown to play a crucial role in the pathogenesis and progression of many malignancies, such as breast, colon, lung, and pancreatic cancer. According to the data from the Gene Expression Omnibus database, miR-21 has been reported to be one of the top 20 differentially expressed microRNAs screened using the Morpheus online tool, and miR-21 has been revealed to regulate a series of biological behaviors in cancer cells, including cell proliferation, migration, invasion, metastasis, and apoptosis. In recent years, gene therapy has emerged as a new therapeutic strategy for cancer treatment. Antisense oligonucleotides have recently been suggested as a novel approach for targeting microRNAs by antisense-based gene silencing. Five phosphorothioate oligonucleotides were designed, synthesized, and screened for anticancer activity. Reverse transcription-polymerase chain reaction was used to detect the relative expression of miR21. Among these 5 sequences, only phosphorothioate oligonucleotide 4 inhibited the proliferation of H1650 cells, and this effect was due to the induction of cancer cell apoptosis by activating the caspase-8 apoptotic pathway. In conclusion, this research confirmed the anticancer activity of phosphorothioate oligonucleotide 4 and revealed the underlying mechanism, which has the potential to be a novel anticancer strategy.

Intercalated combination of chemotherapy and erlotinib for stage IIIA non-small-cell lung cancer: a multicenter, open-label, single-arm, phase II study.

OBJECTIVE: This multicenter, open-label, single-arm, phase II trial evaluated the efficacy and safety of an intercalated combination of erlotinib and gemcitabine/cisplatin or carboplatin in patients with stage IIIA non-small-cell lung cancer (NSCLC). REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT01297101. METHODS: The primary endpoint was the objective response rate (ORR), which includes complete response (CR) and partial response (PR), assessed using RECIST version 1.0 in the intention-to-treat population. Adverse events (AEs) were graded by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Secondary endpoints included the disease control rate, disease-free survival (DFS), overall survival (OS), and safety. Between April 1, 2011, and July 31, 2014, 39 patients with stage IIIA NSCLC received two cycles of intercalated use of erlotinib with gemcitabine/cisplatin or carboplatin. RESULTS: Eighteen patients (46.15%) achieved a PR and no patient achieved a pathologic CR, resulting in an ORR of 46.15% (95% CI 30-63%). Median DFS was 20 months (95% CI 5.26-50.61) and median OS was 25 months (95% CI 15.57-33.39). Patients with EGFR mutations (n=7) had a higher ORR than those with wild-type EGFR (n=9) (85.71% vs 55.56%, P=0.00). Most AEs were CTCAE grade 1 or 2; there were no cases of increased hematologic toxicity or erlotinib-emergent interstitial lung disease observed. CONCLUSION: Two cycles of intercalated neoadjuvant therapy with erlotinib and gemcitabine/cisplatin or carboplatin were effective and safe for patients with stage IIIA NSCLC. This approach should be further explored in larger randomized controlled trials given the lack of a consensus about the best treatment for stage IIIA NSCLC.

A dual-targeted theranostic photosensitizer based on a TADF fluorescein derivative.

Specific diagnosis and therapy of cancer is still a challenge in biomedical research. Photodynamic therapy (PDT) has emerged as a novel therapeutic modality for cancer treatment. However, the traditional PDT photosensitizers often exhibit low specific selectivity. In this study, we have reported a dual-targeted theranostic photosensitizer FL-RGD by covalently conjugating tumor marker cyclic arginine-glycine-aspartic acid tripeptide (RGD) and a fluorescein derivative FL which has a property of thermally activated delayed fluorescence (TADF) and a long triplet lifetime for efficient PDT. The FL-RGD can target tumor tissues and further locate lysosomes of tumor cells to concurrently achieve the cancers' specific diagnosis and efficient treatment. The mechanism of its highly efficient PDT was attributed to the damage of lysosome via 1O2. Besides, FL-RGD has the potential to be utilized in depth imaging and treatment by two-photon excitation. The actual diagnosis performance of FL-RGD was proved by fluorescence imaging of living cells and tumor bearing mice. The therapy performance was proved by MTT assays, fluorescence-activated cell sorting (FACS) analysis and PDT experiments on tumor bearing mice. The research obviously exhibited the potential of FL-RGD for tumor theranostics in vivo and in vitro.

Nitroreductase-Activatable Theranostic Molecules with High PDT Efficiency under Mild Hypoxia Based on a TADF Fluorescein Derivative.

High specificity detection and site-specific therapy are still the main challenges for theranostic anticancer prodrugs. In this work, we reported two smart activatable theranostic molecules based on a thermally activated delayed fluorescence fluorescein derivative. Nitroreductase induced by a mild hypoxia microenvironment of a solid tumor was used to activate the fluorescence and photodynamic therapy (PDT) efficiency by employing the intramolecular photoinduced electron transfer mechanism. A high PDT efficiency under 10% oxygen concentration was achieved, which is better than that of porphyrin (PpIX), a traditional photosensitizer. Such an excellent PDT efficiency can be attributed to lysosome disruption because the theranostic molecule can specifically enter the lysosomes of cells. Importantly, the strategy of targeting the mild hypoxic cells in the edge of tumor tissue could heal the "Achilles' heel" of traditional PDT. We believe that this theranostic molecule has a high potential to be applied in clinical investigation as a theranostic anticancer prodrug.

A dual-modal nanoprobe based on Eu(iii) complex-MnO2 nanosheet nanocomposites for time-gated luminescence-magnetic resonance imaging of glutathione in vitro and in vivo.

Dual-modal fluorescence-magnetic resonance imaging (MRI) techniques have gained great interest in biomedical research and clinical practice, since they integrate the advantages of both imaging techniques and provide a useful approach to simultaneously investigate both molecular and anatomical information at the same biological structures. Herein, we report the construction of a dual-modal time-gated luminescence (TGL)/MRI nanoprobe, BHHBB-Eu3+@MnO2, for glutathione (GSH) by anchoring luminescent ß-diketone-Eu3+ complexes on layered MnO2 nanosheets. The fabricated nanoprobe exhibited very week luminescence and MR signals since the luminescence of the Eu3+ complex was quenched by MnO2 nanosheets and Mn atoms were isolated from water. Upon exposure to GSH, the MnO2 nanosheets were rapidly and selectively reduced to Mn2+ ions, resulting in remarkable enhancements of TGL and MR signals simultaneously. The combination of TGL and MR detection modes enables the nanoprobe to be used for detecting GSH in a wide concentration range (1-1000 µM) and imaging GSH at different resolutions and depths ranging from the subcellular level to the whole body. Furthermore, the as-prepared nanoprobe exhibited a low cytotoxicity and good biocompatibility, rapid response rate, long-lived luminescence, and high sensitivity and selectivity for responding to GSH. These features allowed it to be successfully used for the TGL detection of GSH in human sera, TGL imaging of GSH in living cells and zebrafish, as well as dual-modal TGL/MR imaging of GSH in tumor-bearing mice. All of these results highlighted the applicability and advantages of the nanoprobe for detecting GSH in vitro and in vivo.

Bimodal Phosphorescence-Magnetic Resonance Imaging Nanoprobes for Glutathione Based on MnO2 Nanosheet-Ru(II) Complex Nanoarchitecture.

Bimodal fluorescence-magnetic resonance imaging (MRI) technique has shown great utilities in bioassays because it combines the advantages of both optical imaging and MRI to provide more sufficient information over any modality alone. In this work, on the basis of a MnO2 nanosheet-Ru(II) complex nanoarchitecture, a bimodal phosphorescence-MRI nanoprobe for glutathione (GSH) has been constructed. The nanoprobe, Ru(BPY)3@MnO2, was constructed by integrating MnO2 nanosheets with a phosphorescent Ru(II) complex [Ru(BPY)3](PF6)2 (BPY = 2,2'-bipyridine), which resulted in complete phosphorescence quenching of the Ru(II) complex, accompanied by very low longitudinal and transverse relaxivity. Upon exposure to GSH, the reduction of MnO2 nanosheets by GSH triggers a recovery of phosphorescence and simultaneously produces a number of Mn2+ ions, a perfect MRI contrast agent. The as-prepared nanoprobe showed good water dispersion and biocompatibility and a rapid, selective, and sensitive response toward GSH in the phosphorescence and MR detection modes. The practicability of the nanoprobe was proved by time-gated luminescence assay of GSH in human serum, phosphorescent imaging of endogenous GSH in living cells, zebrafish, and tumor-bearing mice, as well as the MRI of GSH in tumor-bearing mice. The research outcomes suggested the potential of Ru(BPY)3@MnO2 for the bimodal phosphorescence-MRI sensing of GSH in vitro and in vivo.

CCD and RSM optimization approach for antioxidative activity and immune regulation in head kidney of yellow catfish (Pelteobagrus fulvidraco) based on different lipid levels and temperatures.

Yellow catfish (Pelteobagrus fulvidraco) is an important economic cultured fish in China. Here we report antioxidative activity and immune regulation in head kidney using a central composite design based on water temperature (20-34 °C) and dietary lipid (2-17%). Response values were optimized using response surface methodology to maximize the immune response and relieve oxidative stress. The experiment was conducted under laboratory conditions and lasted for seven weeks. The results showed that the linear effects of lipid level on superoxide dismutase (SOD, and lysozyme (LYZ) activity, and malondialdehyde (MDA) content in head kidney, respiratory burst activity (RBA) of head kidney macrophages, and cumulative mortality of fish infected by Streptococcus iniae (S. iniae) were significant (P < 0.05). Similarly, the linear effects of water temperature on SOD activity, MDA content, and cumulative mortality were significant (P < 0.05). In addition, the quadratic effects of water temperature and lipid level on all experimental response values were significant (P < 0.05), and no interactive effect was found between water temperature and lipid level (P > 0.05). High water temperature and high lipid diet significantly reduced the antioxidative activity and immune response in head kidney, and increased MDA content, which caused increased mortality of the S. iniae-infected fish. The adjusted R2 values for SOD activity, MDA content, LYZ activity, RBA, phagocytic activity, and cumulative mortality regression models were 0.76, 0.85, 0.87, 0.79, 0.64, and 0.87, respectively. The optimal combination of water temperature and lipid level was 26.9 °C and 7.7%, at which good antioxidative activity and immune regulation were achieved, with reliability of 0.878. This combination was close to the optimal combination of water temperature and lipid level for growth performance (27.5 °C and 9.2%) reported previously. Thus, the optimal combination may not only promote growth, but also enhance antioxidant and immune levels.

Flexible, Mechanically Durable Aerogel Composites for Oil Capture and Recovery.

More than 30 years separate the two largest oil spills in North American history (the Ixtoc I and Macondo well blowouts), yet the responses to both disasters were nearly identical in spite of advanced material innovation during the same time period. Novel, mechanically durable sorbents could enable (a) sorbent use in the open ocean, (b) automated deployment to minimize workforce exposure to toxic chemicals, and (c) mechanical recovery of spilled oils. Here, we explore the use of two mechanically durable, low-density (0.1-0.2 g cm(-3)), highly porous (85-99% porosity), hydrophobic (water contact angles >120°), flexible aerogel composite blankets as sorbent materials for automated oil capture and recovery: Cabot Thermal Wrap (TW) and Aspen Aerogels Spaceloft (SL). Uptake of crude oils (Iraq and Sweet Bryan Mound oils) was 8.0 ± 0.1 and 6.5 ± 0.3 g g(-1) for SL and 14.0 ± 0.1 and 12.2 ± 0.1 g g(-1) for TW, respectively, nearly twice as high as similar polyurethane- and polypropylene-based devices. Compound-specific uptake experiments and discrimination against water uptake suggested an adsorption-influenced sorption mechanism. Consistent with that mechanism, chemical extraction oil recoveries were 95 ± 2 (SL) and 90 ± 2% (TW), but this is an undesirable extraction route in decentralized oil cleanup efforts. In contrast, mechanical extraction routes are favorable, and a modest compression force (38 N) yielded 44.7 ± 0.5% initially to 42.0 ± 0.4% over 10 reuse cycles for SL and initially 55.0 ± 0.1% for TW, degrading to 30.0 ± 0.2% by the end of 10 cycles. The mechanical integrity of SL deteriorated substantially (800 ± 200 to 80 ± 30 kPa), whereas TW was more robust (380 ± 80 to 700 ± 100 kPa) over 10 uptake-and-compression extraction cycles.

Differential proteomic profiling in human spermatozoa that did or did not result in pregnancy via IVF and AID.

PURPOSE: To identify biochemical markers in men with idiopathic infertility and normal sperm counts. EXPERIMENTAL DESIGN: We obtained proteomic profiling proteins in human spermatozoa following successful or unsuccessful pregnancy via assisted reproductive technology (ART) using 6-plex tandem mass tag (TMT) isobaric mass spectrometry. Our study design consisted of two groups: 1. The semen of 6 men whose sperm resulted in a clinical pregnancy following ART and 6 men whose semen did not result in a clinical pregnancy following ART. The results of differentiated mass spectrometry were validated by Western blotting. RESULTS AND DISCUSSION: A total of 2,045 proteins were detected in our cohort. 21 proteins were found to be differentially expressed (>1.2-fold) in men whose sperm resulted in a clinical pregnancy and those that did not. Using the results of bioinformatics analysis and Western Blotting, three proteins (A2LD1, ATP1B3 and FBXO2) were shown to have the same differential pattern (p<0.05) that was observed in the mass spectrometry analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Proteomics may help identity a select cohort of men with abnormal semen parameters and aide infertility diagnoses.