Bioaccumulation of polycyclic aromatic hydrocarbons and their human health risks depend on the characteristics of microplastics in marine organisms of Sanggou Bay, China.

Microplastics pose a threat to marine environments through their physical presence and as vectors of chemical pollutants. However, the impact of microplastics on the accumulation and human health risk of chemical pollutants in marine organisms remains largely unknown. In this study, we investigated the microplastics and polycyclic aromatic hydrocarbons (PAHs) pollution in marine organisms from Sanggou Bay and analyzed their correlations. Results showed that microplastic and PAHs concentration ranged from 1.23 ± 0.23 to 5.77 ± 1.10 items/g, from 6.98 ± 0.45 to 15.07 ± 1.25 µg/kg, respectively. The microplastic abundance, particularly of fibers, transparent and color plastic debris, correlates strongly with PAH contents, indicating that microplastics increase the bioaccumulation of PAHs and microplastics with these characteristics have a significant vector effect on PAHs. Although consuming seafood from Sanggou Bay induce no carcinogenic risk from PAHs, the presence of microplastics in organisms can significantly increases incremental lifetime cancer risk of PAHs. Thus, microplastics can serve as transport vectors for PAHs with implications for the potential health risks to human through consumption. This study provides new insight into the risks of microplastics in marine environments.

Physiological and transcriptomic analysis reveals the toxic and protective mechanisms of marine microalga Chlorella pyrenoidosa in response to TiO2 nanoparticles and UV-B radiation.

Concerns have been raised regarding the adverse effects of nanoparticles (NPs) on marine organisms, as an increasing number of NPs inevitably enter the marine environment with the development of nanotechnology. Owing to the photocatalytic properties, TiO2 NPs' toxicity may be aggravated by enhanced UV-B resulting from stratospheric ozone depletion. However, the molecular mechanisms of phytoplankton in response to TiO2 NPs under UV-B remains poorly understood. In this study, we integrated whole transcriptome analysis with physiological data to provide understanding on the toxic and protective mechanisms of marine Chlorella pyrenoidosa in response to TiO2 NPs under UV-B. The results indicated that the changes in gene expression could be related to the growth inhibition and TiO2 NP internalization in C. pyrenoidosa, and several molecular mechanisms were identified as toxicity response to TiO2 NPs and UV-B. Differential expression of genes involved in glycerophospholipids metabolism indicated that cell membrane disruption allowed TiO2 NPs to enter the algal cell under UV-B exposure, although the up-regulation of genes involved in the general secretory dependent pathway and the ATP-binding cassette transporter family drove cellular secretion of extracellular polymeric substances, acting as a barrier that prevent TiO2 NP internalization. The absence of changes in gene expression related to the antioxidant system may be responsible for the severe oxidative stress observed in algal cells following exposure to TiO2 NPs under UV-B irradiation. Moreover, differential expression of genes involved in pathways such as photosynthesis and energy metabolism were up-regulated, including the light-harvesting, photosynthetic electron transport coupled to photophosphorylation, carbon fixation, glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that more energy and metabolites were supplied to cope with the toxicity of TiO2 NPs and UV-B. The obtained results provide valuable information on the molecular mechanisms of response of marine phytoplankton exposed to TiO2 NPs and UV-B.

Tensile Property of 7075 Aluminum Alloy with Strengthening Layer by Laser Remelting-Cladding Treatment.

The Ni60-SiC-CeO2 strengthening layer with deep remelting pools was constructed on the surface of 7075 aluminum alloy using the laser remelting-cladding processing method, and a soft and hard interphase was prepared on the matrix by the interval of laser remelting, which was inspired by soft-hard interphase structure with excellent crack inhibition performance from the natural world. The microstructure and microhardness of the remelting region and the remelting-cladding region of the strengthening layer were studied. The tensile characteristics of two distinct strengthening layers were investigated in the laboratory. The results showed that the grain size of remelting pools is finer, and the microhardness is higher than that of the matrix, which makes crack propagation more difficult. In addition, the results show that the strengthening layer has compact and flawless microstructure and has been metallurgically integrated with the matrix, and the microhardness of the regions treated by laser cladding and laser remelting-cladding has been improved obviously. Toughness has improved, as has the problem of toughness reduction after cladding ceramic particles. The sample's strength is also significantly greater than that of the untreated sample.

Effect of Reticulate Unit Spacing on Microstructure and Properties of Biomimetic 7075 Aluminum Alloy by Laser Cladding.

In the context of energy conservation and emission reduction, more and more attention has been paid to the development of lightweight metal materials with both high strength and high toughness. Inspired by the non-smooth surface of natural organisms, a biomimetic surface with various spacing reticulate units of 7075 aluminum alloys was modified by laser cladding. The microstructure, microhardness and tensile properties of the various spacing units with CeO2-SiC-Ni60 were studied. The finer microstructure and the higher microhardness of various spacing units in comparison with that of 7075 aluminum alloys were obtained, no matter the strip-like treated region or the cross-junction region. Moreover, the best combination of strength and toughness of the biomimetic sample with 2.5 mm spacing reticulate unit was discussed. Finally, by combining the microstructure, XRD phase change, thermal gradient effect, thermal expansion coefficient difference and hard phase strengthening mechanism, it was concluded that the 2.5 mm spacing reticulate unit had the best ability to inhibit crack propagation, and the dispersive hard phases of Al3Ni2 and SiC played a major role in stress release of the matrix.

Demonstration of 100-Gbit/s 32-QAM signal transmission in a radio-over-fiber system with 2-bit DAC.

In this Letter, a low-cost radio-over-fiber (RoF) system at the Ka band based on a low-resolution digital-to-analog converter (DAC) is proposed and investigated. The noise shaping (NS) technique is adopted to suppress the in-band quantization noise induced by the low-resolution DAC. To evaluate the performance of the proposed RoF system, the transmission of a 80/100-Gbit/s dual-polarization 16/32-QAM signal over 20-km single-mode fiber (SMF) and 1-m 2 × 2 multi-in multi-out (MIMO) wireless link coupled with a 2/3/4-bit DAC is experimentally demonstrated. The results show that the bit error rate (BER) of the signal generated by the 2-bit DAC can be effectively reduced by more than one order of magnitude when noise shaping is applied.

Cadmium-sulfide/gold/graphitic-carbon-nitride sandwich heterojunction photocatalyst with regulated electron transfer for boosting carbon-dioxide reduction to hydrocarbon.

Developing the heterogeneous photocatalysts with high performance for carbon dioxide (CO2) conversion to solar fuels is remarkably significant for reducing the atmospheric CO2 level and achieving the target of carbon neutrality through the artificial photosynthesis strategies. However, it remains a great challenge for most of the photocatalysts to achieve the CO2-to-hydrocarbon conversion via a multi-proton coupled multi-electron reduction process. In this work, the cadmium-sulfide/gold/graphitic-carbon-nitride (CdS/Au/g-C3N4) heterojunction photocatalyst with sandwich nanostructures is designedly constructed by a selective two-step photodeposition process. The better separation of photogenerated electrons and holes in CdS/Au/g-C3N4 heterojunction creates the higher density of surface photogenerated electron, dynamically accelerating the multi-electron reduction of CO2. Moreover, the selective photodeposition of CdS on Au/g-C3N4 affords sufficient electron-enriched Sδ- active sites which are more beneficial to the provision of H adatoms. These advantages jointly improve the photocatalytic CO2 conversion to methane (CH4) via a multi-proton coupled multi-electron reduction process. The CH4 yield rate on CdS/Au/g-C3N4 photocatalyst is about twice that of CdS/g-C3N4, while g-C3N4 and Au/g-C3N4 only produce CO. The total electron utilization for CO2 reduction on CdS/Au/g-C3N4 photocatalyst is 6.9 times that of g-C3N4. Furthermore, the CdS/Au/g-C3N4 photocatalyst exhibits high stability in consecutive cycles of CO2 reduction reaction. The photocatalytic mechanism is proposed on the basis of in situ spectrographic analyses together with other detailed characterizations.

Probes and drugs that interfere with protein translation via targeting to the RNAs or RNA-protein interactions.

Protein synthesis is critical to cell survival and translation regulation is essential to post-transcriptional gene expression regulation. Disorders of this process, particularly through RNA-binding proteins, is associated with the development and progression of a number of diseases, including cancers. However, the molecular mechanisms underlying the initiation of protein synthesis are intricate, making it difficult to find a drug that interferes with this process. Chemical probes are useful in elucidating the structures of RNA-protein complex and molecular mechanism of biological events. Moreover, some of these chemical probes show certain therapeutic benefits and can be further developed as leading compounds. Here, we will briefly review the general process and mechanism of protein synthesis, and emphasis on chemical probes in examples of probing the RNA structural changes and RNA-protein interactions. Moreover, the therapeutic potential of these probes is also discussed to give a comprehensive understanding.

MYC modulators in cancer: a patent review.

INTRODUCTION: The important role of MYC in tumorigenesis makes it particularly important to design MYC modulators. Over the past decade, researchers have raised a number of strategies for designing MYC modulators, some of which are already in clinical trials. This paper aims to review the patents of MYC modulators. AREAS COVERED: The important biological relevance of c-MYC and the regulation pathways related to c-MYC are briefly introduced. Base on that, the MYC modulators reported in published patents and references primarily for cancer treatment are outlined, highlighting the structures and biological activities. EXPERT OPINION: There has been a growing awareness of finding and designing MYC modulators as novel anticancer drugs over recent years. Patents involving the discovery, synthesis, and application of MYC modulators are particularly important for further development in this field. Although finding direct MYC inhibitors or binders is challenging, MYC cannot be simply defined as an undruggable target. There is still substantial evidence proving the concept that MYC modulators can benefit to the treatment of both human hematological malignancies and solid tumors. More efforts should be taken to improve the activity and specificity of MYC modulators.

Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid⁻Protein Interaction.

G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.

Switchable Ferro-, Ferri-, and Antiferromagnetic States in a Piezo- and Hydrochromic Metal-Organic Framework.

The Mn(II) metal-organic framework with a viologen-based tetracarboxylate ligand exhibits reversible optical (color) and magnetic changes concomitant with stimuli-induced electron transfer from carboxylate to viologen. Compression causes a magnetic transformation from ferro- to ferrimagnetic, while water release/reuptake switches the magnetic behavior between ferro- and antiferromagnetic.

Design, Synthesis, and Evaluation of Novel p-(Methylthio)styryl Substituted Quindoline Derivatives as Neuroblastoma RAS (NRAS) Repressors via Specific Stabilizing the RNA G-Quadruplex.

The human proto-oncogene neuroblastoma RAS ( NRAS) contains a guanine-rich sequence in the 5'-untranslated regions (5'-UTR) of the mRNA that could form an RNA G-quadruplex structure. This structure acts as a repressor for NRAS translation and could be a potential target for anticancer drugs. Our previous studies found an effective scaffold, the quindoline scaffold, for binding and stabilizing the DNA G-quadruplex structures. Here, on the basis of the previous studies and reported RNA-specific probes, a series of novel p-(methylthio)styryl substituted quindoline (MSQ) derivatives were designed, synthesized, and evaluated as NRAS RNA G-quadruplex ligands. Panels of experiments turned out that the introduction of p-(methylthio)styryl side chain could enhance the specific binding to the NRAS RNA G-quadruplex. One of the hits, 4a-10, showed strong stabilizing activity on the G-quadruplex and subsequently repressed NRAS's translation and inhibited tumor cells proliferation. Our finding provided a novel strategy to discover novel NRAS repressors by specifically binding to the RNA G-quadruplex in the 5'-UTR of mRNA.

Efficacy of Chinese patent medicine Tian Gui Capsule in patients with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex hormonal disorder and one of the most common reproductive endocrinology abnormalities in women. Recently, many studies have been conducted assessing Chinese herbal medicine as an alternative treatment for women with PCOS, it is, therefore, worthwhile to analyze and observe the curative effects of traditional Chinese medicine treatment in PCOS. OBJECTIVE: To evaluate the efficacy of the Chinese patent medicine Tian Gui Capsule, in women with PCOS and compare its effects with metformin and ethinyl estradiol plus cyproterone acetate (Diane-35). DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A total of 47 PCOS outpatients from the Obstetrics and Gynecology Hospital of Fudan University were randomly divided into 3 groups. Patients in group A (n=19) were given Tian Gui Capsule, patients in group B (n=17) were given metformin, and patients in group C (n=11) were given Diane-35. The 3 groups of patients were treated for 3 months. MAIN OUTCOME MEASURES: Serum testosterone (T), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-S) levels, free androgen index (FAI), fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitive index (ISI) and left and right ovary volumes of the 3 groups were evaluated before and after treatment . RESULTS: After 3 months of treatment, when compared with before treatment data, group A patients showed decreased serum T and SHBG levels, FAI, FINS, and left and right ovary volumes (P<0.05), and increased serum DHEA-S (P<0.05), while the FPG level showed no significant change. Although the level of serum T and FINS among the 3 groups after the treatment were similar, group A demonstrated better results than group B in reducing the FAI and increasing the serum SHBG, but less significant results than group C besides, group B was the only group showed improved insulin sensitivity. Although the level of FPG of the 3 groups after treatment were similar, group C had the most increased FPG. CONCLUSION: The effects of Tian Gui Capsule on hyperandrogenism are not as significant as Diane-35, but more effective than metformin. The effects of Tian Gui Capsule on hyperinsulinemia are not as significant as metformin but better than Diane-35. Tian Gui Capsule treats PCOS by regulating ovarian functions and reducing blood insulin level without inhibiting the function of the hypothalamic-pituitary-ovarian axis. Further studies with larger sample size are needed to confirm the above results.

[Prelimary exploration on Chinese medicine syndrome type distribution in patients with polycystic ovary syndrome].

OBJECTIVE: To explore the Chinese medicine syndrome type distribution in patients with polycystic ovary syndrome (PCOS) and its relationship with sexual hormones. METHODS: Chinese medicine syndrome types of 212 PCOS patients were differentiated and sorted by adopting fuzzy mean C clustering method, and their relationship with the indices of sexual hormones detected on the 3rd to 5th day of menstrual cycle was analyzed, with the values got from 20 healthy women for controls. RESULTS: Intermingling syndromes were commonly seen in PCOS patients. Shen-deficiency syndrome (presented in 64 patients) and Gan-qi stagnancy syndrome (61 patients) were the dominance, accounting for 30.2% and 28.8% respectively, significantly higher than that of other syndromes (P < 0.05), which were Pi-deficiency syndrome (41 patients, 19.3%), phlegm-dampness syndrome (33 patients, 15.6%) and blood stasis syndrome (13 patients, 6.1%). Levels of estradiol (E2), testosterone (T), luteinzing hormone (LH), dehydroiso-androsterone (DHEA-S) and prolactin (PRL) were higher, while the level of sexual hormone binding protein (SHBG) was lower in PCOS patients than those in control, follicular stimulating hormone (FSH) level in patients of Shen-deficiency syndrome and phlegm-dampness syndrome was high than that in control (P < 0.05 and P < 0.01). However, no significant differences were found in comparing the various sexual endocrinal indices between patients with different syndrome types (P > 0.05). Besides, the level of PRL was positively correlated with LH and E2 levels in patients. CONCLUSION: Chinese medicine syndromes presented in patients with PCOS are mostly intermingling, Shen-deficiency and Gan-stagnancy are the basic syndromes, and there is some correlation between syndrome type and sexual hormone levels.

HPV E6 down-regulation and apoptosis induction of human cervical cancer cells by a novel lipid-soluble extract (PE) from Pinellia pedatisecta Schott in vitro.

AIM OF THE STUDY: To evaluate the cytotoxicity and apoptosis induction effects of a novel lipid-soluble extract (PE) from Pinellia pedatisecta Schott on CaSki, HeLa and HBL-100 cells. Particularly, the effect of PE on HPV E6 gene expression was tested, and the mechanism of its apoptosis induction effect was also studied. MATERIALS AND METHODS: Cell viability was measured by the MTT assay. DAPI staining and flow cytometric analysis (FCM) were used to identify apoptotic cells in PE-treated CaSki, HeLa, and HBL-100 cells. Expression of the HPV E6 gene in CaSki and HeLa cells was detected by real-time RT-PCR and western blot analysis. Apoptosis-associated genes were examined by RT-PCR and western blot analysis in CaSki cells. RESULTS: PE inhibited the growth of CaSki and HeLa cells in a time- and dose-dependent manner, but it had no obvious inhibiting effect on HBL-100 cells except at a relatively high dose (500 µg/mL). PE could induce apoptosis in CaSki and HeLa cells in a time-dependent manner but not in HBL-100 cells. HPV E6 mRNA and protein were decreased significantly by PE. Caspase-8, caspase-3, Bax, P53 and P21 mRNAs as well as proteins were increased while Bcl-2 mRNA and protein were decreased significantly by 24 h of PE treatment. CONCLUSIONS: PE can function as a tumor suppressor by inducing apoptosis in human cervical cancer cells but it has little side effect on normal cells. It probably acts via mitochondria-dependent and death receptor-dependent apoptotic pathways. HPV E6 may be the key target of its action.

[Effect of pinellia extract on HeLa cell line in vitro and associated mechanism].

OBJECTIVE: To investigate the effect of Pinellia extract (PE) on HeLa cell line and to study its associated mechanisms, in order to provide theoretical foundations for its applying in clinical prevention and treatment of cervical disease. METHODS: HeLa cell line was incubated in media containing different concentrations of PE. Growth of cells was observed and photo-generated with inverted phase microscope; cell activity was detected by MTT assay; cell apoptosis detected by flow cytometry, protein expression of proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA) was detected by immuno-cytochemistry, and protein expression of Bcl-2 was determined by immunofluorescence. RESULTS: PE showed obvious inhibition on the proliferation of HeLa cells, cell apoptosis appeared after PE treatment in a time and dose dependent manner; PCNA and Bcl-2 protein expressions reduced significantly after being effected by PE for 24 h. CONCLUSIONS: PE can obviously inhibit the growth and induce the apoptosis of HeLa cells, and its mechanism is possibly realized through down-regulating the expressions of PCNA and Bcl-2. The study set a primary experimental base for further studying the action mechanism of PE and developing new anti-tumor agents.

[Effects of beta-sitosterol on microtubular systems in cervical cancer cells].

OBJECTIVE: To investigate beta-sitosterol's inhibitory effects on SiHa cells' growth, and the effects on microtubular system in SiHa cell. METHODS: Proliferation inhibition of SiHa cell line was evaluated by MTT assay. Cell cycle of SiHa cells treated with beta-sitosterol was analyzed by flow cytometry. The expression and distribution of microtubule and microtubule associated protein 2 in SiHa cells were investigated by confocal microscopy. Immunoblotting analysis was used to determine tubulin alpha, microtubule associated protein 2, and the proportion of polymerization of tubulin. RESULTS: beta-sitosterol could obviously inhibit the proliferation of SiHa cells, and induce the accumulation of cells in S phase (rather than the G2/M phase) and mitotic arrest in the cell cycle. Confocal microscopy showed an abnormal microtubular network in SiHa cell treated with beta-sitosterol for 5 days, and the expression of microtubule associated protein 2 was marked down-regulated. Further analysis by immunoblotting confirmed the down-regulation of beta-sitosterol on the expression for both microtubule associated protein 2 and tubulin alpha. Moreover, beta-sitosterol reduced the proportion of polymerization of microtubule in a time-dependent manner. CONCLUSION: beta-sitosterol could down-regulate the expression of tubulin alpha and microtubule associated protein 2 in SiHa cells, and inhibit the microtubular polymerization. Our results suggested an anti-microtubule characteristic of beta-sitosterol which might contribute to the proliferation inhibition of SiHa cells.

[Effect of Chinese herbal treatment on the efficiency of blocking CD antigen and on prolactin and progesterone in women with recurrent spontaneous abortion].

OBJECTIVE: To explore the effect of Chinese herbal medicine Baotai Granule (BTG, a self-made preparation) on CD antigen blocking efficiency, prolactin (PRL) and progesterone (P) in patients with recurrent spontaneous abortion (RSA). METHODS: Thirty-four women suffered from RSA were treated with BTG, twice every day, 1 package (10 g) in each time by orally intake. Changes of the efficiency of serum blocking antibody in them to the CD antigen in their husband's peripheral T-lymphocytes before and after treatment were observed. And the changes of blood levels of PRL and P were also monitored. RESULTS: Fetus had successfully protected in 30 women (88.2%), in them, the efficiency of blocking to CD3, CD4 and CD8 after treatment were all higher than that before treatment, and levels of PRL and P in peripheral blood increased along with the increase of gestational age, while no obvious change was found in those who failed to complete pregnancy. CONCLUSION: Chinese herbal medicine could protect the fetus by regulating the response between endocrine and immunity network during pregnancy.