Abstract
Efficient extraction of oxygen from ambient waters played a critical role in the development of early arthropods. Maximizing gill surface area enhanced oxygen uptake ability but, with gills ...necessarily exposed to the external environment, also presented the issue of gill contamination. Here we document setae inserted on the dorsal surface of walking legs of the benthic-dwelling middle Cambrian
Olenoides serratus
and on the gill shaft of the Late Ordovician
Triarthrus eatoni
. Based on their physical positions relative to gill filaments, we interpret these setae to have been used to groom the gills, removing particles trapped among the filaments. The coordination between setae and gill filaments is comparable to that seen among modern crustaceans, which use a diverse set of setae-bearing appendages to penetrate between gill filaments when grooming. Grooming is known relatively early in trilobite evolutionary history and would have enhanced gill efficiency by maximizing the surface area for oxygen uptake.
Our current research aims to evaluate the efficiency of a flavor enhancer, maltol (produced by heating ginseng) against cisplatin‐evoked cardiotoxicity by establishing cisplatin‐induced heart injury ...in vivo and H9C2 rat cardiomyocyte model. The cisplatin‐treated mice at 3 mg/kg for four times on the 7th, 9th, 11th and 13th day, and in them appeared a serious cardiac damage accompanied with the increase in indicators of heart damage. Multiple exposure of 3 mg/kg for four times of cisplatin increased cardiac cells apoptosis with increased expression of Bax and cleaved‐caspase 3, and decreased expression of Bcl‐2. Interestingly, supplement of maltol at doses of 50 and 100 mg/kg for 15 days significantly suppressed the cardiac disturbance. In cultured H9C2 cells, maltol enhanced PI3K/Akt expression level during cisplatin treatment, and reduced cisplatin‐induced apoptosis. Notably, inhibition of PI3K/Akt by LY294002 and HY‐10249A lessened the efficacy of maltol. In mice, maltol apparently induced PI3K/Akt in heart tissues and protected against cisplatin‐induced cardiotoxicity. In conclusion, maltol exerted the protective effects against cisplatin‐induced cardiotoxicity, at least partially by inhibiting the activation of PI3K/Akt signaling pathways in cardiomyocytes, to ease oxidative stress, and alleviate reactive oxygen species‐mediated apoptosis.
A systematic study on ligand-to-ligand charge-transfer (LLCT) properties of three closely related metal–organic frameworks (MOFs) is presented. These compounds are formulated as MnL(4,4′-bpy)(H2O) ...n ·nCH3CN (1), MnL(bpe)0.5(DMF) n ·2nH2O (2), and MnL(bpa)(H2O) n ·2nH2O (3) (L = dimethylthio-tetrathiafulvalene-bicarboxylate, 4,4′-bpy = 4,4′-bipyridine, bpe = 1,2-bis(4-pyridyl)ethene, bpa = 1,2-bis(4-pyridyl)ethane). The X-ray single-crystal diffractions show that complexes 1–3 are all two-dimensional (2-D) coordination polymers with different frameworks in crystal lattices. Charge-transfer (CT) interactions within these MOFs are visually apparent in colors and vary according to the conjugated states of the bipyridine ligands (4,4′-bpy, bpe, and bpa). Theoretical calculations show that the charge transfer occurs from ligand L to bipyridine. The intensity of the LLCT is in the order of 2 > 1 > 3 investigated by theoretical calculations and ESR, which indicates that the intensity of CT is related to the bipyridyl conjugated state. Photocurrent responses of these compounds are consequently studied, and the results are in agreement with the intensity of charge transfer and linearly related to the LLCT energy.
Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects ...with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
Heat stress (HS) reaction is a stress response caused by adverse conditions. Currently, the incidence of reproductive malignancies particularly in males has been constantly increasing. This work ...investigated the effects of saponins derived from the stems and leaves of Panax ginseng (GSLS) on testicular injury induced by scrotal hyperthermia in mice. GSLS (150, 300 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43°C for 18 min on seventh day. HS induced a significant loss of multinucleate giant cells, desquamation of germ cells in destructive seminiferous tubules. Moreover, HS reduced the serum testosterone, testicular tissue superoxide dismutase activity and glutathione (GSH) content, while significantly enhanced the production of malondialdehyde (p < .05). GSLS exhibited the protective potential against HS‐induced injury not only by modulating Bcl‐2 family and caspase protease family, but also by suppressing the protein levels of heme oxygenase‐1 (HO‐1), heat shock protein 70 (HSP70), hypoxia inducible factor‐1α (HIF‐1α) and activation of Mitogen‐activated protein kinase (MAPK) signaling pathways (p < .05). In conclusion, we clearly demonstrated that GSLS exhibited a significant protective effect against HS‐induced testicular dysfunction, mainly the inhibition of oxidative stress associated apoptosis partly via regulation of the MAPK signaling pathway.
Cancer is a leading cause of human mortality. Given that it is difficult for conventional therapeutic approaches to effectively eradicate tumors and inhibit their recurrence and metastasis, new ...therapeutic strategies for solving this problem are urgently needed. In this work, we report the development of a two-dimensional titanium carbide nanocomposite drug delivery system. The system can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system. A surface modification engineering strategy has been elaborately designed to realize the multifunctionalization of an MXene, Ti
3
C
2
. In this strategy, the nanocomposite drug delivery system (Ti
3
C
2
@Met@CP) was established
via
layer by layer adsorption of metformin (Met) and compound polysaccharide (CP) on the surface of Ti
3
C
2
nanosheets. Among these materials, the synthesized (AlOH)
4
−
-functionalized Ti
3
C
2
nanosheets possess strong near-infrared absorption (extinction coefficient of 36.2 L g
−1
cm
−1
), high photothermal conversion efficiency (∼59.6%) and effective singlet oxygen generation (
1
O
2
). Compound polysaccharide (CP) is a new immunomodulator formed by mixing lentinan, pachymaran and tremella polysaccharides in optimal proportions. Especially, the decoration of CP onto the Ti
3
C
2
nanosheets endows Ti
3
C
2
with a well-defined shell, improves its tumor site aggregation and biocompatibility, and activates the host's immune functions. The synergistic eradication and inhibition of tumor recurrence and metastasis have been systematically evaluated by
in vivo
and
in vitro
experiments.
A nanocomposite drug delivery system (Ti
3
C
2
@Met@CP) can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system.
Two plateaus and a following bump in the X-ray light curve of GRB 170714A have been detected by the Swift/X-ray Telescope, which could be very significant for the central engine of gamma-ray bursts ...(GRBs), implying that the origin of this burst might be different from those of other ultra-long GRBs. We propose that merging two neutron stars into a hyper-massive quark star (QS) and then collapsing into a black hole (BH), with a delay time around 104 s, could be responsible for these X-ray components. The hyper-massive QS is initially in a fluid state, being turbulent and differentially rotating, but would solidify and release its latent heat, injecting it into the GRB fireball (lasting about 103 s during the liquid-solid phase transition). A magnetic field as high as ∼1015 G can be created by dynamo action of the newborn liquid QS, and a magnetar-like central engine (after solidification) supplies significant energy for the second plateau. More energy could be released during a fall-back accretion after the post-merger QS collapses to a BH, and the X-ray bump forms. This post-merger QS model could be tested by future observations, with either advanced gravitational wave detectors (e.g., advanced LIGO and VIRGO) or X-ray/optical telescopes.
Background Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment. Study Design ...Multicenter, prospective, randomized, controlled trial. Setting & Participants 176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0 g/24 h, and estimated glomerular filtration rate > 30 mL/min/1.73 m2. Intervention Mycophenolate mofetil (MMF) group: MMF, 1.5 g/d, for 6 months and prednisone, 0.4 to 0.6 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months. Outcomes The primary end point was complete remission rate at 6 and 12 months. Results At baseline, median estimated glomerular filtration rates were 90.2 and 94.3 mL/min/1.73 m2 and mean proteinuria was protein excretion of 2.37 and 2.47 g/24 h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant ( P = 0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant ( P = 0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group. Limitations Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up. Conclusions MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.
Abstract
DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly ...selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.
Graphical Abstract
Graphical Abstract
Thiazole orange-based small molecules engineered to possess the functional property of two-directional and multi-site interactions with G4–DNA structures achieving excellent G4-target selectivity and in vivo antitumor activity against breast cancer.
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