The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19. Higher viral loads soon after symptom onset indicate ...the need for isolation strategies different from those used for the earlier SARS epidemic.
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•Humic acid-metal complexation drives the aggregation of Humic acids at neutral condition.•Heavy metal ions exhibit larger extent of aggregation than common metal ions under neutral ...pH condition.•The H-bonds and other weak interactions can facilitate the coagulation of Humic acid.
Humic acid (HA) exerts a variety of significant environmental and geochemical influences on the soils, sediments and aqueous environments. The interaction with metal ions induces strong HA-metal complexation, thus effecting the transport of the toxic metals as well as the colloidal aggregation of HA. In the present work, we systematically report and analyze the aggregation mechanisms of HAs in solutions filled with different heavy cations (Ag+, Cd2+ and Cr3+) or common metal ions (Na+, Ca2+ and Al3+) under neutral and low pH conditions by using molecular dynamic simulations. We aim to explore the effects of pH, metal ions type and other possible weak interactions on the aggregation capabilities of HA. Scrutiny of the simulation results showed that the aggregation of HAs under neutral condition was driven by the HA-metal complexation which combined the effects of electrostatic attraction and inter-molecular bridging between cations and COO– groups. Larger extent of aggregation was found in heavy metal ions compared with the common ones. On the other hand, under low pH condition, due to the protonation states of carboxyl and phenolic group, the aggregation of HAs was stabilized mainly by weak forces, such as hydrogen bonds between different functional groups. In addition, other weak interactions such as the hydrophilic and hydrophobic effects, the cation-π interactions have also been proposed to be progressive effects on the coagulation behavior. Our computational studies give supplement to the experimental observation and provide insights into the intrinsic mechanisms of the aggregation behavior of HAs and their complexation with metal ions. Such computational modelling supplied a highly effective tool for qualitatively evaluating their roles in environmental remediation.
Drug combination therapies employing dual-drug delivery systems offer an effective approach to reduce disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. ...Herein, a dual-drug delivery system based on nanogel-incorporated injectable hydrogel (NHG) was designed for sequential local delivery of combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) for antiangiogenesis and anticancer combination therapy. The injectable hydrogel was prepared for loading and quick release of hydrophilic drug CA4P, while the pH and redox stimuli-responsive nanohydrogels were incorporated into the injectable hydrogel by pH-responsive boronate ester bond for sustained long-term DOX delivery. The dual-drug-loaded NHG system released CA4P and DOX sequentially and exhibited high inhibitory activities on the cancer cell proliferation in vitro. It displayed superior therapeutic efficacy in vivo with only one single injection. Immunohistochemistry analyses suggested a synergistic therapeutic effect through tumor vascular collapse caused by CA4P and tumor cell apoptosis induced by DOX. The combination therapy of antiangiogenic and cytotoxic drugs using NHG delivery system offers a promising approach for improved cancer therapeutic efficacy. The nanogel-embedded injectable hydrogel can be employed as a universal drug carrier for local dual-drug delivery with sequential release behaviors by simple injection.
The effects of La-Ce rare earth treatment on inclusions， continuous casting castability and steel properties of Q345D structural steel were analyzed by field test. The results showed that the alloy ...yield of RE in Q345D structural steel was 21. 5%. Compared with the heats without RE addition， the desulfurization rate increased by 37. 5%， and the unit inclusion density decreased from 80. 16/mm2 to 60. 78/mm2 . The inclusions in molten steel before La-Ce rare earth treat ment were mainly MgO-Al2O3-CaO composite inclusions. The modification effect of La-Ce rare earth treatment on small size （ D≤5 μm ） inclusions was more obvious. Small size inclusions were modified into （La-Ce-S） and （La-Ce-Al-S-O） rare earth inclusions. La-Ce rare earth treatment can significantly reduce the aspect ratio of MnS inclusions in steel， so that the morphology of MnS inclusions after rolling was closer to ellipse without long linear， which was the main reason for the increase of transverse impact energy of Q345D structural steel by 20
Ordered heterojunction nanocap arrays composed of the bilayer film Ag/ZnS were prepared onto ordered two-dimensional polystyrene bead arrays by magnetron control sputtering, and the surface ...morphologies were tuned by changing the ZnS thickness. When the ZnS thickness varied from 10 to 30 nm with a Ag thickness of 5 nm, the roughness of the bilayer film Ag/ZnS increased obviously. The UV–VIS spectra showed the shifted LSPR peaks with ZnS thickness, which was attributed to the changes of the electron density as confirmed by Hall effect analysis. SERS observations confirmed the charge transfer process for the varied electromagnetic couplings when the ZnS thickness changed.
In Alzheimer’s disease, ion permeability through the ionic channel formed by Aβ peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of ...the toxic ionic channel by Aβ peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aβ1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aβ peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aβ1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aβ1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aβ1-28 peptides’ pores to the cell.
The efficacy and safety of multikinase inhibitor anlotinib have been confirmed in the treatment of advanced non-small cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor ...lethality mediated by anlotinib were not fully elucidated, and the underlying mechanisms related to resistance remain largely elusive.
Cell viability, colony formation, apoptosis and tumor growth assays were performed to examine the effect of anlotinib on lung cancer cells in vitro and in vivo. The punctate patterns of LC3-I/II were detected by confocal microscopy. HUVECs motility was detected using Transwell and scratch wound-healing assay. To visualize the microvessels, tubular formation assay was performed. The expression of LC3-I/II and beclin-1 and the changes of JAK2/STAT3/VEGFA pathway were detected by western blotting. The VEGFA levels in tumor supernatant were measured by ELISA.
Anlotinib treatment decreased cell viability and induced apoptosis in Calu-1 and A549 cells. Moreover, anlotinib induced human lung cancer cell autophagy in a dose- and time-dependent manner. Blocking autophagy enhanced the cytotoxicity and anti-angiogenic ability of anlotinib as evidenced by HUVECs migration, invasion, and tubular formation assay. Co-administration of anlotinib and chloroquine (CQ) further reduced VEGFA level in the tumor supernatant, compared with that of anlotinib or CQ treatment alone. When autophagy was induced by rapamycin, the JAK2/STAT3 pathway was activated and VEGFA was elevated, which was attenuated after deactivating STAT3 by S3I-201. Further in vivo studies showed that anlotinib inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3/VEGFA pathway, and CQ enhanced this effect.
Anlotinib induced apoptosis and protective autophagy in human lung cancer cell lines. Autophagy inhibition further enhanced the cytotoxic effects of anlotinib, and potentiated the anti-angiogenic property of anlotinib through JAK2/STAT3/VEGFA signaling.
The lamellar graphene oxide (GO) membranes could offer well-defined 2D nanochannels for fast water permeation and excellent ions rejection. In this work, lamellar GO membranes were constructed by ...stacking GO nanosheets layer-by-layer via molecular simulation. The effect of hydroxyl and epoxy groups as well as their content on the desalination performance in lamellar GO membranes were investigated by molecular dynamics simulation. The transport and separation mechanisms of water molecules and ions passing through the lamellar GO membranes with different functional group were also revealed from thermodynamic and hydrogen bond network. It is found that water flux in GO membranes would be influenced by the order of water molecules and the hydrogen network formed between functional groups and water molecules. GOOH membranes showed a higher Na+ rejection rate than Cl− at high hydroxyl contents.
•The transport mechanism of water molecules through the lamellar GO membranes was discussed by hydrogen bond network and its dynamics•The separation mechanism for ions passing through GO membranes were investigated from thermodynamic and hydration layer around ions•Water flux in GOO membranes was mainly affected by the order of water molecules•Water flux in GOOH membranes was mainly influenced by the hydrogen network
Pregnancy is known to be a risk factor for venous thromboembolism (VTE). We report the case of a pregnant patient with difficult to diagnose iliac vein thrombosis, establishing a definite diagnosis ...by clues of great saphenous vein reflux.
A 37-year-old G1P0 woman at 35 weeks of assisted twin gestation presented with a complaint of persistent left lower limb edema and tenderness. A vascular ultrasound was used to examine the bilateral lower limb. Doppler of left lower extremity revealed continuous great saphenous vein reflux. Right saphenofemoral veins demonstrated venous stasis and no reflux. Unilateral continuous great saphenous vein reflux suggested left iliac veins obstruction or extrinsic compression. Anterograde venography showed a completely occlusive filling defect of the left external iliac vein, which is the definitive diagnosis of acute deep venous thrombosis. The patient underwent a cesarean delivery following inferior vena cava filter (IVCF) placement, and no signs of deep venous thrombosis (DVT) or pulmonary embolism (PE) were reported after delivery.
In pregnant women with suspected deep vein thrombosis, it is imperative to assess the presence of unilateral continuous great saphenous vein reflux.
Objective To learn the molecular characteristics of influenza B Victoria lineage (Bv) and evaluate the influenza B spread trend about the epidemic. Methods Based on the Guangdong Influenza ...Surveillance Networks (GDISN) to selected the Bv with space-time sampling, the nucleotide sequences of HA/NA genes were detected. The evolution and mutations of both genes were analyzed in homology with MEGA 7.026和SPSS 23.0, in evolutionary tree with neighbor-joining method, in selective evolution with Datamonkey 2.0. Results The nucleotide homologies of HA/NA genes in the 2021 strains were statistically different from these of the 2020's (P < 0.01), in which the those of HA genes in 17 strains isolated in the second half of 2021 were up to (99.28±0.25)% compared with these in the vaccine strain B/Austria/1359417/2021. As to HA genes, the epitope A (H137N/Q, A142T and R148G), B (P159L and N162K) and D (S209N/D and T211A) were mutated, therefore the 2020 and 2021 strains in Guangdong were respectively classified into Clade B
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