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Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two important gut microbiota-generated protein-bound uremic toxins. The present study aims to explore the alterations of serum IS and pCS concentrations, their production, and daily removal in end-stage renal disease (ESRD).A case-controlled study was conducted based on 11 patients with ESRD and 11 healthy volunteers. The metabolic processes for IS and pCS were compared in these two groups, including gut microbiome, fecal indole and p-cresol, indole-producing bacteria and p-cresol-producing bacteria, serum total IS and pCS concentrations, and their daily removal by urine and spent dialyzate.Compared with healthy controls, patients with ESRD exhibited higher relative abundance of the indole-producing bacteria Escherichia coli (P .001) and Bacteroides fragilis (P = .010) and p-cresol-producing bacteria Bacteroides fragilis (P = .010) and Bacteroides caccae (P = .047). The predicted functional profiles of gut microbiome based on 16S rRNA gene PhyloChip analysis showed that the microbial tryptophan metabolism pathway (map00380, P = .0006) was significantly enriched in patients with ESRD. However, the fecal precursors indole (P = .332) and p-cresol concentrations (P = .699) were comparable between the two groups. The serum IS (P .001) and pCS (P .001) concentrations were far higher in patients with ESRD than those in healthy controls, whereas the daily total removal by urine and dialyzate was much lower for the former than that for the latter (P = .019 for IS, P = .016 for pCS).The present study showed serious IS and pCS accumulation in patients with ESRD, with significant expansion of indole-producing bacteria and p-cresol-producing bacteria, upregulation of the bacterial tryptophan metabolism pathway, and greatly increased serum IS and pCS concentrations, whereas significant decline of daily IS and pCS removal.

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward (R)-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40°C (AnDDH), 50°C (HcDDH) and 60°C (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40°C. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording (S)-diols and (1S, 2S)-trans-diols in ≥99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans-1,2-indandiol on a 100 ml scale reaction, (S, S)- trans-1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10-300 mmol•L-1) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69-98% yields of (R)-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.

BACKGROUND Drug extravasation is a complication of totally implantable access port (TIAP) use and could cause tissue injury and sustained organ dysfunction. Therefore, the clinical management of children with TIAP is challenging. CASE SUMMARY This was a case of extravasation of a chemotherapeutic drug (paclitaxel) from an implantable infusion port in a 23-mo old child. After fully evaluating the skin at the site of extravasation, the nurse continued to use the infusion port to complete the follow-up chemotherapeutic course. The skin around the infusion port was red, and showed no ulceration, swelling, or induration at discharge. CONCLUSION Since children are more active and often noncompliant, it is necessary to appropriately train pediatric nurses caring for individuals with TIAPs, and any abnormal situation should be timely addressed.

Morphology-controlled electrocatalysts with the ability of CO2 adsorption/activation, mass transfer, high stability and porosity are much desired in electrochemical CO2 reduction reaction (CO2RR). Here, three kinds of multi-dimensional nanostructures (i.e., hollow sphere, nanosheets and nanofibers) have been successfully produced through the modulation of porphyrin-based covalent organic frameworks (COFs) with various modulators. The obtained nanostructures with high-stability, large surface-area, and single metal sites enable efficient CO2RR into CH4. Notably, they all exhibit higher FECH4 (hollow sphere, 68.2%; nanosheet, 64.2% and nanofiber, 71.0%, -0.9 V) than COF-366-Cu (43.0%, -0.9 V) after morphology control. Noteworthy, the FECH4 of COF-366-Cu (HS) keeps higher than 52.4% over a wide potential range from -0.9 V to -1.1 V and the achieved FECH4+C2H4 (82.8%, -0.9 V) is superior to most of reported COFs and copper-based electrocatalysts. This work paves a new way in the exploration of COF-based multi-dimensional nanostructures applicable in efficient CO2RR to CH4.

The controllable construction of light-emitting organometallic supramolecular materials integrating stimulus responses and biological applications is still a major challenge today. In this work, em...

Facile fabrication of low cost photocatalyst with enhanced activity and high atomic utilization has been in increasing demand for solar energy usage and/or conversion. In this work, a series of mesoporous carbon nitride nanosheets with enlarged specific surface area were synthesized via an inorganic acid-assisted exfoliation method without any soft or hard templates. Ultralow loading of downsized noble metal Pt was anchored on these porous nanosheets and warranted enhanced photocatalytic activity. The formation of mesoporous nanosheets in carbon nitride was expected to boost mass transfer and shorten charge carrier transfer route during photocatalytic reaction. Characterizations revealed that the enlarged conductivity and photocurrent of carbon nitride nanosheets also contributed to the enhanced H2 evolution. The maximum H2 production rates of 172.92 μmol/h and 321 μmol/h could be achieved over these nanosheets derived from melamine and urea under visible light irradiation, which are 10.92 and 2.22 folds as high as that of corresponding bulk carbon nitride, respectively. This exfoliation method was demonstrated to be an efficient and universal method for the preparation of carbon nitride nanosheets with mesoporous structure and high atomic utilization of co-catalyst for H2 evolution from water.

Blast furnace slag (BFS), as a byproduct from manufacturing iron, served as a cost-effective raw material for preparation of hydroxyapatite-zeolite composite material (HAP-ZE); this research introduces a way of synthesizing hydroxyapatite-zeolite composite material (HAP-ZE) using BFS with alkaline fusion and hydrothermal treatment. According to analysis with XRD, FT-IR, BET, ICP, FE-SEM, EDX and elemental mapping, the major phases in the HAP-ZE composite material synthesized under the most desirable conditions (at aging time of 6 h and at Ca/P ratio (starting gel) = 1.67) were identified to be zeolite and HAP with molar ratio of Ca/P = 1.61, Si/Al = 1.31, Na/Al = 1.75 and with a mean surface area of 44.22 m2.g−1. Moreover, the research found that the minor metals (Mg, Fe, K, etc.) generated from BFS have little influence on the synthesis of HAP-ZE. The thus obtained HAP-ZE material has a great adsorption performance in removing Mn2+, NH4+ and phosphate ions mixed in water, on grounds of the higher ion-exchange capacities and abundantly existing Ca2+ ions in HAP-ZE structure. This novel process makes synthesizing HAP-ZE composite material from BFS possible and lays a great foundation for effective application of BFS.

In this work, an edible cellulose-based antibacterial material was prepared by cross-linking α-cellulose and kanamycin sulfate via glutaraldehyde to form kanamycin sulfate-glutaraldehyde-cellulose. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and X-ray diffraction results indicated that the kanamycin sulfate molecule was cross-linked with the molecular chain of cellulose. The optimal mass ratio of kanamycin sulfate to α-cellulose was 1:100 and the degree of substitution reached 1.11%. The optimal kanamycin sulfate-glutaraldehyde-cellulose material showed an excellent inhabitation against both Gram-positive and Gram-negative bacteria. Meantime, the optimal kanamycin sulfate-glutaraldehyde-cellulose had a marked resistance to gastric acid and had low cell cytotoxicity. To promote the application of the kanamycin sulfate-glutaraldehyde-cellulose material, the porous microspheres were prepared via the sol-gel method. The particle size of the homogeneous porous microspheres is mainly distributed between 1.5 and 2.0 μm. Therefore, the kanamycin sulfate-glutaraldehyde-cellulose described herein is a potential edible, eco-friendly, potent, stable, inexpensive, and antibacterial carrier material for delivering drugs, proteins, or vaccines.

Sunitinib is one of the first-line multi-tyrosine kinase inhibitors for metastatic renal cell carcinoma, and resistance to sunitinib continues to be a limiting factor for the successful treatment. As interleukin-6 (IL-6) is overexpressed in sunitinib-resistant cells, the purpose of this study was to explore the potential of IL-6 inhibition with tocilizumab, an IL-6 receptor inhibitor, to overcome resistance. In vitro, two sunitinib-resistant renal cell carcinoma cell lines (Caki-1 and SN12K1) were treated with tocilizumab. A mouse subcutaneous xenograft model was also used. Cell viability was studied by MTT assay, and apoptosis by morphology and ApopTag. Expression of IL-6, vascular endothelial growth factor (VEGF), and Bcl-2 was analyzed by qPCR. In vitro, tocilizumab induced significant cell death, and reduced the expression of IL-6, VEGF, and Bcl-2 in sunitinib-resistant cells. However, the in vitro findings could not be successfully translated in vivo, as tocilizumab did not decrease the growth of the tumors.

Immobilization of soil cadmium (Cd) has been the strategy mostly used in remediation of Cd-contaminated arable soil. However, Cd might be remobilized after the immobilization process through the acid-soluble and complexation effects. Development of agronomic management technologies to prevent soil Cd remobilization after the immobilization process was an important pathway to control the food safety of agricultural products in soils with the immobilized Cd. In this study, the ammonia (NH4+-N) and nitrate (NO3−-N) forms with concentrations of 60, 90, and 150 mg-N kg−1 soil were performed for evaluating their effects on Cd remobilization with planted or unplanted treatments and Cd accumulation in tissues of edible amaranth (Liuye). With an initial soil palygorskite-bound fraction Cd concentration of 0.6 mg kg−1, bioavailable Cd in rhizosphere soils and Cd in crop shoots respectively increased from 11.4 to 20.6 μg kg−1 (dry soil weight) and 6.92 to 14.92 mg kg−1 (dry plant weight) in planted NH4+-N treatments, while significantly lower concentrations of bioavailable Cd in rhizosphere soils and Cd in crop tissues were observed with planted NO3−-N treatments. Compared with that of planted NO3−-N treatments, decreasing pH value (i.e., 7.64 to 7.18) induced by root proton efflux during the absorption of NH4+-N, enhancive organic/amino acid (oxalic acid, lactic acid, l-proline, and so on) secretion from roots, and increasing abundance of bacteria distributed in phyla Proteobacteria, Cyanobacteria, and Bacteroidetes with Cd mobilization ability in rhizosphere soils were the main reasons found in this study for the higher Cd remobilization in soils and Cd accumulation in crop under NH4+-N treatments. Moreover, the direct effect of NH4+-N on remobilization of immobilized Cd by upregulating the expression abundances of genes associated with pyruvate metabolism and amino acids metabolism was more significant than that of NO3−-N. In summary, the use of NO3−-N as preferred N fertilizer was more efficient to ensure the food safety of agricultural products than that of NH4+-N in Cd-contaminated arable soil after immobilization process.

The increasing demand for high-purity rare earths and their compounds induced the separation technology of rare earths promotion. In this work, the mixtures of sec-nonylphenoxy acetic acid (CA100) and alkylated phosphine oxides (Cyanex923 and Cyanex925) were used as extractants instead of single CA100 for high-efficiency extraction of rare earths from chloride medium. Compared with single CA100 system, the mixtures of CA100 and Cyanex923/Cyanex925 could improve the extraction selectivity of Yttrium (Y) from the lanthanoids based on their separation factors. The evident synergistic effects on lanthanum (III) with CA100 and Cyanex923 were investigated by using the methods of slope analysis and constant mole to determine the extraction reaction. The reaction product, equilibrium constants, formation constants, and the thermodynamic functions were determined. The synergistic extraction of lanthanum (III) with CA100 and Cyanex923 was proved to be endothermically driven.

Tailoring the Ti coordination states in titanosilicate zeolites to simultaneously improve feedstock conversion and maximize the target product selectivity remains a challenge in the pursuit of high-performance catalysts for selective oxidation reactions. Herein, we provide a facile strategy to synthesize hierarchical anatase-free TS-1 (MFI-type) zeolites with tetrahedrally coordinated (TiO4) and octahedrally coordinated Ti species (TiO6). The TiO4 species provide high epoxide selectivity, while the TiO6 species afford improved alkene conversion. This strategy is achieved by synergistically using an L-lysine-assisted approach and a two-step crystallization; the two-step crystallization approach prevents the formation of anatase TiO2, while L-lysine stabilizes the TiO6 species and ensures efficient incorporation of TiO6 into the anatase-free TS-1 zeolites. Compared with their conventional counterparts, which only contain TiO4 species, the as-prepared TS-1 zeolites (Si/Ti = 36.9) result in a higher 1-hexene conversion (33%), higher TON value (153), and comparable epoxide selectivity (95%). This synthetic strategy provides avenues to tailor the amount and distribution of Ti species in titanosilicate zeolites to achieve high catalytic performances in various processes.

A type of strontium and amorphous calcium phosphate dipped premixed injectable tricalcium silicate-based dental root canal sealer was developed as the following protocols. A powder mixture containing tricalcium silicate, strontium carbonate (6, 8, 10, and 12 wt%), zirconia (20 wt%), calcium chloride (6 wt%), and amorphous calcium phosphate (ACP) (5 wt%) was mixed with liquid polyethylene glycol 400 (PEG 400) at a liquid-to-powder ratio of 0.5 mL/g and mechanically ground using a planetary ball to obtain the premixed injectable calcium silicate-based sealer. The sealer’s physicochemical property and cytocompatibility were evaluated in vitro. Quantitative data were expressed as mean ± standard deviation, and Student's t-test or a one-way analysis of variance (ANOVA) test were carried out at significant differences with P

Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Methods Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Results Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Conclusion Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways., Pts can relieve asthma by suppressing oxidative stress through the AMPK/Sirt1 and Nrf2/HO‐1 signaling pathways. Thus, Pts might be a potential anti‐inflammatory drug for the treatment of asthma.

Natural bio-enzyme catalysts usually exhibit unexpected performances for many significant reactions, which are worthy of reference. Here we report artificial metal-sulfur-carbon (M-S-C) mimic-enzyme catalysts based on bionic design. The catalysts combine metal centers and functional ligands, which realize the universal fabrication of phase and adjustable dimension. The synthesized catalysts inherit the highly active and selective feature of bio-enzyme catalysts. When directly used for carbon dioxide electroreduction reaction, the Sn-S-C catalyst exhibits high selectivity for formate (Faradaic efficiency >95%), as well as a continuous stability over 120 h at a high current density of 740 mA cm−2, greatly outperforming the reported catalysts for formate formation. The catalytic sites and pathways are probed with in-situ Fourier transform infrared (FTIR) spectra, in-situ Raman spectra and synchrotron-radiation X-ray photoelectron spectra. These results break the inherent conundrum which is impossible to simultaneously realize activity and durability under high selectivity. Our findings offer a versatile strategy to inherit from nature and integrate different components, thus designing efficient catalysts for various challenging reactions and energy conversions via a natural sustainable way.

A semiconductor nano-material was prepared, and its degradation efficiency of zearalenone (ZEN) was studied. The photocatalytic material graphitic carbon nitride (g-C3 N4 ) was synthesized by the traditional method of hot cracking. Its structure was characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The photocatalytic degradation experiment showed that under the irradiation of ultraviolet (UV) lamp (254 nm, including 185 nm), g-C3 N4 could induce photocatalytic effect, which provided a new method for the degradation of ZEN in real powder samples. The experimental conditions of photocatalytic degradation of the primary reference material of ZEN and ZEN in real powder samples were explored. And the degradation products of ZEN were analyzed after high-performance liquid chromatography-mass spectrometry (HPLC-MS). Under each optimal experimental conditions, the degradation rate on primary reference material of ZEN and ZEN in real powder samples was 96.0% and 50.0%, respectively. The results in this work provide a theoretical reference and practical basis for the photocatalytic degradation of mycotoxin in real powder samples by g-C3 N4 .

Penthiopyrad is a novel succinate dehydrogenase inhibitor that has one chiral center and exists a metabolite, 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide in its residue definition. An efficient analytical method for the simultaneous determination of penthiopyrad enantiomers and its metabolite in eight matrices were developed using modified quick, easy, cheap, effective, rugged, safe method, coupled with chiral stationary phase and ultra-high performance liquid chromatography-tandem mass spectrometry. The absolute configuration of penthiopyrad enantiomers was confirmed by polarimetry and electronic circular dichroism. Eight polysaccharide-based chiral stationary phases were evaluated in terms of the enantioseparation of penthiopyrad and separation-related factors (the mobile phase, flow rate and the column temperature) were optimized. To obtain an optimal purification, different sorbent combinations were assessed. The linearities of this method were acceptable in the range of 0.005 to 1 mg/L with R2 > 0.998, while the limits of detection and quantification were 0.0015 mg/kg and 0.01 mg/kg for two enantiomers and its metabolite. The average recoveries of R-(-)-penthiopyrad, S-(+)-penthiopyrad and the metabolite ranged from 75.4 to 109.1, 69.5 to 112.8, and 70.0 to 108.5%, respectively. The intra-day and inter-day relative standard deviations were less than 18.8%. The analytical method was accurate and convenient, which can support their further research on stereoselective degradation, residual monitoring and risk assessment.

During a screening for novel and useful actinobacteria in desert animal, a new actinomycete was isolated and designated strain TRM63209T. The strain was isolated from in vivo of a Blattella germanica in Tarim University in Alar City, Xinjiang, north-west China. The strain was found to exhibit an inhibitory effect on biofilm formation by Candida albicans ATCC 18,804. The strain was observed to form abundant aerial mycelium, occasionally twisted and which differentiated into spiral spore chains. Spores of TRM63209T were observed to be oval-shaped, with a smooth surface. Strain TRM63209T was found to grow optimally at 28 °C, pH 8 and in the presence of 1% (w/v) NaCl. The whole-cell sugars of strain TRM63209T were rhamnose ribose, xylose, mannose, galactose and glucose, and the principal polarlipids were found to be diphosphatidylglycerol, phos-phatidylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, phosphatidylinositol and an unknown phospholipid(L). The diagnostic cell wall amino acid was identified as LL-diaminopimelic acid. The predominant menaquinone was found to be MK-9(H6) (14.64%), MK-9(H2) (19.65%), MK-9(H8) (22.34%), MK-10(H2) (25.37%). The major cellular fatty acids were identified as iso-C16:0, 16:0, anteiso-C15:0, anteiso-C17:0, iso-C15:0 and Sum in Feature 3. Analysis of the 16S rRNA sequence showed that strain TRM63209T exhibits high sequence similarity to Streptomyces bungoensis strain DSM 41781T 98.20%. A multi-locus sequence analysis of five house-keeping genes (atpD, gyrB, rpoB, recA and trpB) and phylogenomic analysis also illustrated that strain TRM63209T should be assigned to the genus Streptomyces. The DNA G + C content of the strain was determined to be 70.2 mol%. Average nucleotide identity (ANI) between strain TRM63209T and S. bungoensis DSM 41781T, Streptomyces phyllanthi PA1-07T, Streptomyces longwoodensis DSM 41677T and Streptomyces caeruleatus NRRL B-24802T were 82.76%, 82.54%, 82.65%, 84.02%, respectively. Digtal DNA-DNA (dDDH) hybridization were 26.30%, 25.10%, 26.20%, 29.50%, respectively. Therefore, it is concluded that strain TRM63209T represents a novel species of the genus Streptomyces, for which the name Streptomyces blattelae is proposed. The type strain is TRM63209T (CCTCC AA 2018093T = LMG 31,403 = TRM63209T).

Purposefully designing the well-defined catalysts for the selective electroreduction of CO2 to C2 H4 is an extremely important but challenging work. In this work, three crystalline trinuclear copper clusters (Cu3 -X, X=Cl- , Br- , NO3- ) have been designed, containing three active Cu sites with the identical coordination environment and appropriate spatial distance, delivering high selectivity for the electrocatalytic reduction of CO2 to C2 H4 . The highest faradaic efficiency of Cu3 -X for CO2 -to-C2 H4 conversion can be adjusted from 31.90 % to 55.01 % by simply replacing the counter anions (NO3- , Cl- , Br- ). The DFT calculation results verify that Cu3 -X can facilitate the C-C coupling of identical *CHO intermediates, subsequently forming molecular symmetrical C2 H4 product. This work provides an important molecular model system and a new design perspective for electroreduction of CO2 to C2 products with symmetrical molecular structure.

A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC50 values of 11.31 ± 3.29 μM, 18.77 ± 6.14 μM and 30.02 ± 3.73 μM, respectively.

The objective of this study was to investigate the single- and multiple-dose pharmacokinetics of chelerythrine (CHE) and its metabolite, dihydrochelerythrine (DHCHE), after oral and IM administrations in pigs.Six crossbreed (Landrace × Large White) female pigs (7-8 weeks old; 24.1 ± 2.6 kg bw) administered oral and IM CHE at a dose of 0.1 mg/kg orally and intramuscularly in a cross-over design. Multiple oral administration was performed at 0.1 mg/kg a time, three times a day at 8-h intervals for three consecutive days. Blood samples were collected from the anterior vena cava and placed into heparinized centrifuge tubes before dosing (time 0 h) and at different times after oral and IM administrations. Pre-treatment plasma was analysed by high-performance liquid chromatography-tandem mass spectrometry.After IM administration, CHE and DHCHE rapidly reached peak concentrations (

This study investigated the effects of applying cellulase and starch on the fermentation characteristics and microbial communities of Napier grass silage after ensiling for 30 d. Three groups were studied: No additives (control); added cellulase (Group 1); and added cellulase and starch (Group 2). The results showed that the addition of cellulase and starch decreased the crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and pH significantly (p < 0.05) and increased water-soluble carbohydrate (WSC) content (p < 0.05). The addition of additives in two treated groups exerted a positive effect on the lactic acid (LA) content, lactic acid bacteria (LAB) population, and lactic acid / acetic acid (LA/AA) ratio, even the changes were not significant (p > 0.05). Calculation of Flieg’s scores indicated that cellulase application increased silage quality to some extent, while the application of cellulase and starch together significantly improved fermentation (p < 0.05). Compared with the control, both additive groups showed increased microbial diversity after ensiling with an abundance of favorable bacteria including Firmicutes and Weissella, and the bacteria including Proteobacteria, Bacteroidetes, Acinetobacter increased as well. For alpha diversity analysis, the combined application of cellulase and starch in Group 2 gave significant increases in all indices (p < 0.05). The study demonstrated that the application of cellulase and starch can increase the quality of Napier grass preserved as silage.

Background Although renal insufficiency and dyslipidemia are known to be closely associated, the effect of kidney function on the size and clinical value of high-density lipoprotein (HDL) particles remains largely unknown, especially in patients with coronary heart disease. Methods A total of 419 coronary heart disease patients and 105 non-coronary heart disease patients were included. HDL particle size, represented by HDL-C/apoA-I, was compared between groups stratified by estimated glomerular filtration rate (eGFR) and Gensini scores using standard Student’s t test and one-way ANOVA. Pearson’s correlation test was performed to analyze the association between eGFR and HDL-C/apoA-I in patients with coronary heart disease. The relationship between HDL particle size and the occurrence of coronary heart disease was explored using Univariate logistic regression analysis. Results In patients with coronary heart disease, between-group analysis revealed that HDL-C/apoA-I increased as eGFR declined, and significance appeared as eGFR declined to under 60 ml/min·1.73 m2 (P 2), those with higher Gensini scores had smaller HDL-C/apoA-I. However, with or without kidney insufficiency, smaller HDL-C/apoA-I was associated with a higher occurrence of coronary heart disease (P Conclusion With the presence of renal insufficiency, HDL-C/apoA1 was higher in patients with coronary heart disease. Lower HDL-C/apoA1 was still associated with a higher occurrence of coronary heart disease, but the original association between lower HDL-C/apoA1 and more severe coronary artery stenosis was lost in patients with renal insufficiency.

Background It was an effective method and research focus to remove recalcitrant organic pollutants by advanced oxidation processes based on persulfate activation with composite material as heterogeneous catalysts. Methods Fe/N co-doped biochar (Fe/N-BC) was synthesized via one-pot calcination method with anhydrous FeCl3, melamine, and grape skin powder as precursors. Characterization results showed that biomass and melamine could anchor iron species on BC matrixes by coordination. Significant findings The Fe/N0.1-BC exhibited significant activities toward peroxymonosulfate (PMS) activation, and 20 mg/L RhB can be degraded completely in 10 min with 0.05 g/L of the material and 0.5 g/L PMS. Electron paramagnetic resonance (EPR) study and free radical quenching experiments indicated that singlet oxygen (1O2), sulfate radicals (SO4•−), and hydroxyl radicals (•OH) were the main reactive oxidizing species, and non-radical mechanism and free radical process were considered to be involved in the degradation of the pollutants. Control experiments revealed that the enhanced active sites were mainly ascribed to rich defects as well as the synergistic effect among Fe and N doping into carbon substrate. The Fe/N-BC owned the merits of environmentally friendly raw materials, easy synthesis, and high activation efficiency, exhibiting splendid prospect for environmental application.

SummaryBackground. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.

Metal sulfides have been universally studied as anode materials for lithium ion batteries (LIBs). Herein, we studied the lithiation storage behavior of a novel metal sulfide PbTiS3 (PTS), which is one of misfit layer compounds (MLCs) including intercalation-type TiS2 layer and conversion-alloying-type PbS layer. In-situ powder X-ray diffraction measurement reveals that the final lithiated product Li22Pb5 can be restored, indicating a reversible conversion-alloying mechanism in PTS. Theoretical calculation indicates the soft PbS interlayers of rock salt structure can hinder the distortion of TiS2 layers upon lithiation, resulting in a high structural integration of PTS anodes as well as a high concentration of intercalated Li ions. Moreover, with the assistance of the strong interfacial C–O–Pb/Ti interaction between PTS and graphene oxide (GO), PTS can be embedded in the conductive GO network which could stabilize PTS structure during long term cycling. Consequently, the fabricated LIBs anode delivers a relatively high reversible capacity (569 mA h g−1 at 2.0 A g−1 after 1000 cycles) and an outstanding high-rate capability. Besides, the assembled lithium ion full battery maintains a capacity retention of 70% after 100 cycles at 0.1 A g−1. This work provides insights into the design of MLCs as next-generation secondary batteries.

Fluensulfone (FSF) becomes increasingly popular because of its nonfumigation application method. However, studies on the metabolic mechanism of FSF in plants are lacking. Here, tomato seedling was cultivated in hydroponic media to investigate the connection among FSF's metabolism in tomato, the regulation of tomato endogenous glycosides, and the elimination of hydrogen peroxide in tomato cells. The accumulation of FSF was only detected in the lower stems of tomatoes; FSF was mainly metabolized into S-glycosylated conjugates in the roots, and the roots were the tissues with the highest metabolite content; and no FSF and metabolites were detected in the upper leaves. In response to FSF stress (2 mg/L for 7 d), the content of sugar and glycosides in the stems of tomato seedlings significantly increased. The amount of some compounds on the pathway related to glucose was affected by FSF. The three precursor compounds (homomethioine, isoleucine, and l-tyrosine) in the pathway of glucosinolate biosynthesis increased significantly under the stress of FSF, which indicates that FSF may compete with them for UGT74B1. Besides, FSF-induced flavonoid glycosides may play a role in the process of removing hydrogen peroxide. This research provides inspiration for the fate of many xenobiotics containing sulfonyl groups in plants.

In this paper, the intermetallic compound (IMC) growth behaviors of Sn/Cu and Sn–0.6SiC/Cu solder under isothermal aging (50, 100, 150, 200 and 250 h) and thermal cycling (300, 600, 900, 1200 and 1500 cycles) were studied. The results manifested that the IMC layer got thicker in Sn/Cu solder and Sn–0.6SiC/Cu solder as the aging time or thermal cycles increased, but the IMC thickness of Sn solder incorporated with silicon carbide nanowires (SiC NWs) was smaller than that of Sn solder in the same condition. According to the adsorption theory, SiC NWs would adsorb on the IMC grains and then reduce the surface tension of IMC, which made for the suppression of IMC growth. Also, SiC NWs could nail at grain boundaries and then prohibit the further growth of IMC grains. Thus, doping 0.6 wt% SiC NWs could reduce the size of IMC grains and decrease the diffusion coefficient of IMC growth, which led to prohibiting the interfacial IMC growth at solder/substrate under isothermal aging. During thermal cycling process, SiC NWs addition was beneficial to decrease the rate of IMC growth at the interface of Sn/Cu solder. Moreover, adding SiC NWs into Sn solder could improve the reliability of solder joints in that there were less cracks formed at IMC layer in Sn–SiC/Cu solder.

Tephrosin is a natural rotenoid isoflavonoid that has been shown to have potent anticancer activities. In this study, we reported the anticancer activity of tephrosin against pancreatic cancer cells. Tephrosin potently suppressed cell viability in various cancer cell lines and promoted apoptosis of PANC-1 and SW1990 pancreatic cancer cells evidenced by enhanced cleavage of caspase-3/-9 and PARP. Further studies showed that tephrosin increased the production of intracellular reactive oxygen species (ROS) and led to mitochondrial membrane potential depolarization, and subsequent cytochrome c release. DNA damage was also identified by increased tail DNA and phosphorylation of H2AX. Intracellular ROS production seems to be essential for the anticancer activity of tephrosin, alleviation of ROS production by ROS scavengers weakened the apoptotic effects of tephrosin. Importantly, in PANC-1 xenografted nude mice, potent antitumor activity and low toxicity of tephrosin were observed. In conclusion, these results indicated that tephrosin could be developed as a potential chemotherapeutic agent for the treatment of human pancreatic cancer.

Metal halide perovskites based on MX6 (M is metal and X is halogen) octahedra have developed into significant materials, extensively used in many fields, such as solid-state lighting, semiconductor, and nonlinear optics. However, the MX5 square pyramid-based hybrid metal halides beyond zero-dimensional (0D) polyhedrons and clusters are rarely reported. Herein, we reported two new isostructural hybrid antimony halides, namely (2cepyH)SbCl4 (1-Cl) and (2cepyH)SbBr4 (2-Br) (2cepy = 1-(2-chloroethyl)pyrrolidine), characterized by 1D polar polyanionic chains formed by corner-sharing SbX5 tetragonal pyramid units. Upon photoexcitation at 340 nm, 1-Cl shows broad, yellow phosphorescence emissions stemming from triplet self-trapped excitons, as proved by its long lifetime (6.85 μs) and the temperature dependences of broadband emission. To our knowledge, this should be the first observation on the broadband emissive properties in the 1D hybrid metal halide constructed by MX5 tetragonal pyramid units. Moreover, second harmonic generation measurements show that the nonlinear optical properties of 2-Br (∼3.2 × KDP) are superior to that of 1-Cl (∼1.8 × KDP). Experimental and calculated data indicate that the bandgap of 1-Cl is larger than that of 2-Br and that the polar inorganic moieties determine their band structures. Our work opens up a new way for constructing broadband emission materials with novel polar frameworks.

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP). After systemic administration, the developed HAL/3BP@X-MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co-localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.

Layered Mn-based oxides are one of the promising cathode materials for potassium-ion batteries (KIBs) owing to their high theoretical capacities, abundant material supply, and simple synthesis method. However, the structural deterioration resulting from the Jahn-Teller effect of Mn ions hinders their further development in KIBs. Herein, a novel Mn-based layered oxide, K0.54Mn0.78Mg0.22O2, is successfully designed and fabricated as KIBs cathode for the first time. It delivers smooth charging/discharging curves with high specific capacity of 132.4 mA·g-1 at 20 mA·g-1 and good high-rate cycling stability with a capacity retention of 84% over 100 cycles at 200 mA·g-1. Combining in-situ X-ray diffraction (XRD) and ex-situ X-ray photoelectron spectroscopy (XPS) analysis, the storage of K-ions by K0.54Mn0.78Mg0.22O2 is revealed to be a solid-solution processes with reversible slip of the crystal lattice. The studies suggest that the rational doping of inactive Mg2+ can effectively suppress the Jahn-Teller effect and provide outstanding structure stability. This work deepens the understanding of the structural evolution of Mn-based layered materials doped with inactive materials during de/potassiation processes.

Background Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of Pten-KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa). Methods Three matched pairs of tissue-specific conditional Pten-KO mouse prostate and WT prostate of litter/cage-mates at 20-22 weeks of age and three pairs of TRAMP NECa versus WT (28-31 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography-tandem mass spectrometry. Results The Pten-KO prostate increased purine nucleotide pools, cystathionine, and both reduced and oxidized glutathione (GSH, GSSG), and gluconate/glucuronate species in addition to cholesteryl sulfate and polyamine precursor ornithine. On the contrary, Pten-KO prostate contained diminished pools of glycolytic intermediates and phosphorylcholine derivatives, select amino acids, and their metabolites. Bioinformatic integration revealed a significant shunting of glucose away from glycolysis-citrate cycle and glycerol-lipid genesis to pentose phosphate cycle for NADPH/GSH/GSSG redox and pentose moieties for purine and pyrimidine nucleotides, and glycosylation/glucuronidation. Implicit arginine catabolism to ornithine was consistent with immunosuppression in Pten-KO model. While also increased in cystathionine-GSH/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at the expense of glycolysis-citrate cycle, the TRAMP NECa increased abundance of many amino acids, methyl donor S-adenosyl-methionine, and intermediates for phospholipids without increasing cholesteryl sulfate or ornithine. Conclusions The aqueous metabolomic patterns in Pten-KO prostate and TRAMP NECa shared similarities in the greater pools of cystathionine, GSH/GSSG redox pair, and nucleotides and shunting away from glycolysis-citrate cycle in both models. Remarkable metabolic distinctions between them included metabolisms of many amino acids (protein synthesis; arginine-ornithine/immune suppression) and cholesteryl sulfate and methylation donor for epigenetic regulations.

Microbial sulfate reduction is largely associated with anaerobic methane oxidation and alkane degradation in sulfate-methane transition zone (SMTZ) of deep-sea cold seeps. How the sulfur cycling is mediated by microbes near SMTZ has not been fully understood. In this study, we detected a shallow SMTZ in three of eight sediment cores sampled from two cold seep areas in the South China Sea. One hundred ten genomes representing sulfur-oxidizing bacteria (SOB) and sulfur-reducing bacteria (SRB) strains were identified from three SMTZ-bearing cores. In the layers above SMTZ, SOB were mostly constituted by Campylobacterota, Gammaproteobacteria and Alphaproteobacteria that probably depended on nitrogen oxides and/or oxygen for oxidation of sulfide and thiosulfate in near-surface sediment layers. In the layers below the SMTZ, the deltaproteobacterial SRB genomes and metatranscriptomes revealed CO2 fixation by Wood-Ljungdahl pathway, sulfate reduction and nitrogen fixation for syntrophic or fermentative lifestyle. A total of 68% of the metagenome assembled genomes were not adjacent to known species in a phylogenomic tree, indicating a high diversity of bacteria involved in sulfur cycling. With the large number of genomes for SOB and SRB, our study uncovers the microbial populations that potentially mediate sulfur metabolism and associated carbon and nitrogen cycles, which sheds light on complex biogeochemical processes in deep-sea environments.

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.

V2CO2 MXene Supported Sc or Mn single atoms are expected to serve as the cost-effective bifunctional catalysts for fuel cells due to its high catalytic activity.

Background Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. Methods Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. Results Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41–1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. Conclusion The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

Bisphenol F (BPF) is a member of endocrine disrupting chemicals (EDCs). As a substitute of bisphenol A (BPA), BPF is widely used in various consumer products, leading to an increased risk of people's exposure. However, there are few studies on the immunotoxicity and mechanism of BPF. This study aimed to investigate the effect of BPF on the secretion of pro-inflammatory cytokines by macrophages and explore its mechanism. In our study, RAW264.7 macrophages were treated with different concentrations of BPF (0, 5, 10 and 20 μM) for 24 h. The results showed that the secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) and the production of lactate were increased in a dose-dependent manner. BPFalso led to the activation of the PI3K-AKT signaling pathway. After pretreatment with glycolysis inhibitor (2-DG) and exposure to BPF (20 μM), the secretion of pro-inflammatory cytokines induced by BPF was inhibited. PI3K inhibitor (LY294002) and estrogen receptor (ER) antagonist (ICI 182,780) could also inhibit the above effects induced by BPF (20 μM). In conclusion, our results suggested that BPF can enhance glycolysis through ER mediated PI3K-AKT signaling pathway, and the enhanced glycolysis further promoted the secretion of pro-inflammatory cytokines. Our research provides basic data for future studies on bisphenol exposure and immunotoxicity.

Objective Resin-based dental adhesion is mostly utilized in minimally invasive operative dentistry. However, improving the durability and stability of resin–dentin bond interfaces remain a challenge. Graphene quantum dots (GQDs) reinforced by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were introduced to modify the resin–dentin bond interfaces, thereby promoting their durability and stability. Methods GQDs, EDC, and EDC+GQDs groups were designed to evaluate the effects of GQDs and EDC on collagenase activity, the interaction of GQDs with collagen, and the resin–dentin interface. First, the effects of GQDs and EDC on collagenase activity was evaluated by Collagenase (EC 3.4.24.3) reacting with its substrate. The interaction of GQDs and EDC with collagen were evaluated by cross-linking degree analysis, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, attenuated total reflection Fourier transform infrared spectroscopy and enzymatic hydrolysis. Second, the acid-etched and rinse adhesive system was used to evaluate the resin–dentin bond on the basis of microtensile bond strength, in situ zymography and fluorescence confocal laser scanning microscopy. Results GQDs could inhibit collagenase activity. GQDs with the aid of EDC could cross-link collagen via covalent bonds and improve the anti-enzymatic hydrolysis of collagen. In the resin–dentin adhesion model, the μTBS of the EDC+GQDs group was significantly higher than the other control groups after thermocycling. The addition of EDC to GQDs could inhibit matrix metalloproteinase activity and promote the integrity of the bonding interfaces after thermocycling. Significance This study presents a novel strategy to modify the resin–dentin interface and provides a new application for GQDs. This strategy has the potential to improve the durability of resin-based restoration in dentistry.

B atoms and cyano groups co-doped graphite carbon nitride with nitrogen vacancies (VN-BC-CN) was explored via one-step in-situ route. A series of comprehensive experiments confirmed that B atoms and cyano groups had been doped into the framework of graphite carbon nitride, forming VN-BC-CN catalyst sample with a large number of nitrogen-vacancy defects. As electron acceptors, B and cyano groups could be used as active sites for nitrogen conversion. The defect level caused by nitrogen vacancy led to red shift of the light absorption edge, which resulted in higher separation efficiency of photo-induced carriers and faster transfer rate of photo-induced electrons for the VN-BC-CN catalyst. This VN-BC-CN catalyst had good photocatalytic nitrogen fixation performance in the ultrapure water without any hole-scavengers. The nitrogen photofixation rate of VN-BC-CN (115.53 μmol g−1 h−1) was 25.5 times that of pure carbon nitride (GCN, 4.53 μmol g−1 h−1). Moreover, NH4+ generation rate hardly decreased after 10 h reaction, and the NH4+ generation rate could reach 79.56 μmol g−1 h−1 in the fifth cycle, showing the good photocatalytic stability of the VN-BC-CN catalyst.

Background Acute kidney injury is common in patients with COVID-19, however mechanisms of kidney injury remain unclear. Since cytokine storm is likely a cause of AKI and glomerular disease, we investigated the two major transcription factors, STAT3 and NF-kB, which are known to be activated by cytokines. Methods This is an observational study of the postmortem kidneys of 50 patients who died with COVID-19 in the Mount Sinai Hospital during the first pandemic surge. All samples were reviewed under light microscopy, electron microscopy, and immunofluorescence by trained renal pathologists. In situ hybridization evaluation for SARS-CoV-2 and immunostaining of transcription factors STAT3 and NF-kB were performed. Results Consistent with previous findings, acute tubular injury was the major pathological finding, together with global or focal glomerulosclerosis. We were not able to detect SARS-CoV-2 in kidney cells. ACE2 expression was reduced in the tubular cells of patients who died with COVID-19 and did not co-localize with TMPRSS2. SARS-CoV-2 was identified occasionally in the mononuclear cells in the peritubular capillary and interstitium. STAT3 phosphorylation at Tyr705 was increased in 2 cases in the glomeruli and in 3 cases in the tubulointerstitial compartments. Interestingly, STAT3 phosphorylation at Ser727 increased in 9 cases but only in the tubulointerstitial compartment. A significant increase in NF-kB phosphorylation at Ser276 was also found in the tubulointerstitium of the two patients with increased p-STAT3 (Tyr705). Conclusions Our findings suggest that, instead of tyrosine phosphorylation, serine phosphorylation of STAT3 is commonly activated in the kidney of patients with COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01173-0.

Despite HER2-targeted cancer treatments have provided considerable clinical benefits, resistance to HER2-targeted agents will inevitably develop. Targeting non-oncogene vulnerabilities including endoplasmic reticulum (EnR) stress has emerged as an attractive alternative approach to improve the efficacy of existing targeted cancer therapies. In the current study, we find that Melatonin sensitizes HER2-positive breast cancer cells to the dual tyrosine kinase inhibitor Lapatinib in vitro. Mechanistically, Melatonin enhances the cytotoxic effects of Lapatinib through promoting excessive EnR stress-induced unfolded protein response (UPR) and ROS overaccumulation. Consistently, the antioxidant N-acetylcysteine remarkably reverses the effects of the drug combination on ROS production, DNA damage and cytotoxicity. Furthermore, Melatonin significantly enhances the anti-tumor effect of Lapatinib in an HCC1954 xenograft model. Meanwhile, Lapatinib resistant HER2-positive breast cancer cells (LapR) display lower basal expression levels of UPR genes and enhanced tolerance to EnR stress with attenuated response to Brefeldin A and Tunicamycin. Importantly, Melatonin also increases the sensitivity of HCC1954 LapR cells to Lapatinib. Together, our findings highlight the potential utility of Melatonin as an adjuvant in the treatment of primary or therapy resistant HER2-positive breast cancer via EnR stress-mediated mechanisms.

In recent years, synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer. However, the development of superb photothermal agents with high drug loading capacity is still highly required. In this work, a hollow mesoporous polyaniline nanoparticle (HPANI NP) has been developed for encapsulating chemotherapeutic drug doxorubicin (DOX) with an remarkable drug loading content as high as 37.5%. Additional PEG modification endowed the drug-loaded HPANI NPs with improved water-dispersibility and bioavailability. Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity, exhibiting highly efficient synergistic cancer treatment. More interestingly, the responsively released DOX molecules could emit strong red fluorescence, which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs. Finally, the as-fabricated NPs showed good biocompatibility and low toxicity, serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy.

GV971 derived from marine acidic oligosaccharides has been used to cure Alzheimer's disease (AD). However, the molecular mechanism of its inhibition of the conformational transition of amyloid β-proteins (Aβ) is still unclear. Herein, molecular dynamics simulations were used to explore the molecular mechanism of the main GV971 components including DiM, TetraM, HexaM, and OctaM to inhibit the conformational conversion of the Aβ42 monomer. It is found that the GV971 components inhibit the conformational transition from α-helix to β-sheet and the hydrophobic collapse of the Aβ42 monomer. In addition, the binding energy analysis implies that both electrostatic and van der Waals interactions are beneficial to the binding of GV971 components to the Aβ42 monomer. Among them, electrostatic interactions occupy the dominant position. Moreover, the GV971 components mainly interact directly with the charged residues D1, R5, K16, and K28 by forming salt bridges and hydrogen bonds, which specifically bind to the N-terminal region of Aβ42.

Combining the advantages of dual-ion batteries (DIBs) and sodium-ion batteries (SIBs), we herein develop a superior sodium-based dual-ion battery (Na-DIB) based on the PTCDA organic anode and ionic liquid (IL) electrolyte. The system shows the highest specific discharge capacity of 177 mAh g-1 at 0.5C and excellent capacity retention over 100% at 2C after 200 cycles. Notably, even at an ultrahigh rate of 20C, the battery still maintains a considerable capacity of 60 mAh g-1 with a coulombic efficiency (CE) close to 100 and 94% capacity retention after 1000 cycles. Moreover, the self-discharge of the system has been investigated and shown to have an extremely low value of 0.18% h-1. Consequently, this work presents an excellent Na-DIB system, which could be a promising candidate for large-scale applications.

Nanozyme is a class of artificial materials that possess enzyme-like activities and can overcome limitations of natural enzymes. However, controllability of the active sites, uniformity of the particles, and dispersion in the physiological media are still challenging for nanomaterial-based nanozymes. In this work, a protein-based nanozyme has been constructed by the encapsulation of hemin into the nanocavity of a recombinant human heavy chain ferritin (Ftn), generating a monodispersed peroxidase-mimetic nanozyme (hemin@Ftn). Hemin@Ftn possesses high peroxidase catalytic activity and high tolerance to the harsh environmental conditions, such as high temperature and chemical denaturant. Remarkably, hemin@Ftn can act as a colorimetric probe for the detection of tumor cells because it can selectively catalyze reactions in tumor cells. This protein-based nanozyme bridges the gap between natural enzymes and nanomaterial-based nanozymes by the incorporation of a catalytically active prosthetic group into a highly stable Ftn.