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There is a close connection between epigenetic regulation, cancer metabolism, and immunology. The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management. As an epigenetic regulator of histone acetylation, panobinostat can induce histone acetylation and inhibit tumor cell proliferation, as well as regulate aerobic glycolysis and reprogram intratumoral immune cells. JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression. Herein, we proposed a chemo-free, epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer. A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor. It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona. The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells (e.g., tumor-associated macrophages). The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization. Consequently, lactic acid production was reduced and angiogenesis inhibited; TAM switched to an anti-tumor phenotype, and the anti-tumor function of the effector CD8+ T cells was reinforced. The strategy provides a potential method for remodeling the tumor immune microenvironment (TIME).

In recent years, the treatment of dye wastewater has attracted widespread attention. Metal-organic frameworks (MOFs) adopt ordered porous structures and abundant active sites, which endorses them promising photocatalysts for the degradation of organic pollutants. In this work, two rare earth MOFs were successfully synthesized by solvothermal method from the reaction of of Eu3+ and Tb3+ salts with an aromatic tetracarboxylic acid H4TPTC (3,3',5,5'-terphenyl tetracarboxylic acid). X-ray single crystal diffraction indicated that the isostructural MOFs exhibited unique di-nuclear [Eu2(COO)4] or [Tb2(COO)4] clusters to construct three-dimensional coordination frameworks with solvent accessible channels along the [110] direction. These two MOFs had good thermal stability up to 400 °C and pH stability in the pH range of 3-9. The negative Zeta potential on the surface of these two complexes were conducive to the selective adsorption and degradation of cationic and neutral dyes, especially the high removal rate of large RhB molecules. For the photocatalytic degradation, mechanism studies showed that ·OH and ·O2- enhanced the sensitization of dyes and the separation of photogenerated carriers, and promoted the efficiency of photocatalytic degradation. This work provides two isomorphic rare earth MOFs adsorbents as well as photocatalysts for the purification of dye wastewater.

Exploring the ratiometric fluorescence biosensing of DNA-templated biemissive silver nanoclusters (AgNCs) is significant in bioanalysis, yet the design of a stimuli-responsive DNA device is a challenge. Herein, using the anti-digoxin antibody (anti-Dig) with two identical binding sites as a model, a tweezer-like DNA architecture is assembled to populate fluorescent green- and red-AgNCs (g-AgNCs and r-AgNCs), aiming to produce a ratio signal via specific recognition of anti-Dig with two haptens (DigH). To this end, four DNA probes are programmed, including a reporter strand (RS) dually ended with a g-/r-AgNC template sequence, an enhancer strand (ES) tethering two same G-rich tails (G18), a capture strand (CS) labeled with DigH at two ends, and a help strand (HS). Initially, both g-AgNCs and r-AgNCs wrapped in the intact RS are nonfluorescent, whereas the base pairing between RS, ES, CS, and HS resulted in the construction of DNA mechanical tweezers with two symmetric arms hinged by a rigid "fulcrum", in which g-AgNCs are lighted up due to G18 proximity ("green-on"), and r-AgNCs away from G18 are still dark ("red-off"). When two DigHs in proximity recognize and bind anti-Dig, the conformation switch of these tweezers resultantly occurs, taking g-AgNCs away from G18 for "green-off" and bringing r-AgNCs close to G18 for "red-on". As such, the ratiometric fluorescence of r-AgNCs versus g-AgNCs is generated in response to anti-Dig, achieving reliable quantization with a limit of detection at the picomolar level. Based on the fast stimulated switch of unique DNA tweezers, our ratiometric strategy of dual-emitting AgNCs would provide a new avenue for a variety of bioassays.

Well recent study confirmed that surface Bronsted acid sites could evidently improve the formation of free hydroxyl radicals of semiconductors and thus enhanced the photocatalytic degradation activ...

Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer’s disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg(−1) · d(−1), ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.

Transcriptional regulatory protein (TRP)-based whole-cell biosensors are widely used nowadays. Here, they were demonstrated to have great potential application in screening cell efflux and influx pumps for small molecules. First, a vanillin whole-cell biosensor was developed by altering the specificity of a TRP, VanR, and strains with improved vanillin productions that were selected from a random genome mutagenesis library by using this biosensor as a high-throughput screening tool. A high intracellular vanillin concentration was found to accumulate due to the inactivation of the AcrA protein, indicating the involvement of this protein in vanillin efflux. Then, the application of this biosensor was extended to explore efflux and influx pumps, combined with directed genome evolution. Elevated intracellular vanillin levels resulting from efflux pump inactivation or influx pump overexpression could be rapidly detected by the whole-cell biosensor, markedly facilitating the identification of genome targets related to small-molecule transmembrane transport, which is of great importance in metabolic engineering.

Background: We recently developed the Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system. Our preliminary study demonstrated that the CatLet score better predicted clinical outcomes than the SYNTAX score. The current study aimed at assessing whether 3 clinical variables (CVs) – age, serum creatinine, and left ventricular ejection fraction (LVEF) – improved the performance of the CatLet score in outcome predictions in patients with acute myocardial infarction (AMI). Methods: This study was a post hoc study of the CatLet score validation trial. Primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), and secondary endpoints were all-cause deaths and cardiac deaths. Results: Over 1,185 person-years (median [interquartile range], 4.3 [3.8–4.9] years), there were 64 MACCEs (20.8%), 56 all-cause deaths (18.2%), and 47 cardiac deaths (15.2%). The addition of the 3 CVs to the stand-alone CatLet score significantly increased the Harrell’s C-index by 0.0967 (p = 0.002) in MACCEs, by 0.1354 (p < 0.001) in all-cause deaths, and by 0.1187 (p = 0.001) in cardiac deaths. When compared with the stand-alone CatLet score, improved discrimination and better calibration led to a significantly refined risk stratification, particularly at the intermediate-risk category. Conclusions: CatLet score had a predicting value for clinical outcome in AMI patients. This predicting value can be improved through a combination with age, serum creatinine, and LVEF (http://www.chictr.org.cn; unique identifier: ChiCTR-POC-17013536).

Using visible light as a driving force and molecular oxygen as a green oxidant, we developed bis(oxazoline)-Ni(acac)2 catalyzed asymmetric α-hydroxylation of β-keto esters under low photosensitizer loading, and the protocol enabled an efficient transformation to provide the desired chiral α-hydroxy-β-keto esters in high yields (up to 99%) and enantioselectivities (up to 99% ee) at room temperature.

Density functional theory (DFT) calculations are used to explore the adsorption characteristics and degradation mechanism of sulfacetamide on anatase TiO2(101) and (001) surfaces. The most probable adsorption configuration was firstly determined by comparing the adsorption energies and structural bond lengths before and after adsorption. After adsorption, some of the bond lengths are elongated. We have proposed about six possible degradation pathways of sulfacetamide, such as branch chain breaking, benzene ring dihydroxylation, amino substitution and sulphur nitrogen bond breaking. And the relevant degradation processes are studied in detail. Based on the calculated results, we conclude that the TiO2(001) surface is more suitable for the degradation of sulfacetamide considering its much smaller energy barriers in several degradation paths than the TiO2(101). Among all the six possible degradation paths, we find that the hydroxyl radical attacks of C(1), C(3) and N(6) atoms of the (001) surface and the C(4) atom of (101) surface sulfacetamide are most probable reaction pathways due to their much smaller energy barriers, i.e. 7.7, 26.1 kcal mol−1 and 14.6, 23.4 kcal mol−1 indicating that these reactions can easily take place in room temperature. Our computational results are not only consistent with the experimental results of sulfacetamide degradation, but also reveal the possible microscopic mechanisms of the photocatalytic reaction.

A series of branched dodecyl phenol polyoxyethylene ethers (b-DPEOn) were successfully synthesized via alkylation and ethylene oxide addition reactions. The alkylation reaction was conducted by using a branched internal olefin as the raw material. Furthermore, the conversion rate of the branched dodecene was measured to be 98.1% and the selectivity towards branched dodecyl phenol (b-DP) was 95.9%. Moreover, b-DPEOn (b-DPEO7, b-DPEO10, b-DPEO12) were obtained via the reaction of ethylene oxide with b-DP. Notably, b-DPEO10 can efficiently reduce the surface tension of water below 31.55 mN m−1 at the critical micelle concentration (cmc) and the cmc value in water was approximately 1.3 × 10−2 g L−1 at 25 °C. The preferable wetting ability of b-DPEO10 was superior to that of commercialized dodecyl phenol polyoxyethylene ether (c-DPEOn), so it will be promoted and used in the textile and pesticide industries.

Recently, experimentalists have developed a green and efficient method to synthesize pyrazole-fused quinones through light-induced tetrazole-quinone 1,3-dipole cycloadditions. However, the underlying microscopic mechanisms remain to be clarified. In this work, we have employed several electronic structure calculation methods (MS-CASPT2, CASSCF, DFT) to systematically explore the microscopic mechanism of related light-induced reactions and deactivation pathways. Upon excitation with ultraviolet light, one of the original reactants 2-(4-fluorophenyl)-5-phenyl-2

Expanding the family of lanthanide terpyridine coordination polymers has yielded eighteen new complexes with two different phases, Ln(TPC)2(HCOO)(H2O) (Ln-1) and Ln(TPC)(HCOO)2 (Ln-2) (Ln = Sm–Lu, except Tm). Both structures are composed of lanthanide cations interconnected by 2,2′:6′,2′′-terpyridine-4′-carboxylate ligands to yield one-dimensional chain topologies. However, the incorporation of an additional crystallographically unique decorative TPC ligand into Ln-1 gives rises to a distinct phase. The encapsulation of both metal- and ligand-based phosphors within single coordination polymers leads to dual-emission of the afforded materials. Furthermore, judicious lanthanide doping in heterometallic Ln-1 and Ln-2 allows for fine-tuning the photoluminescent colours over a wide range of gamut. Such a combination showcases the capability to fine-tune the emission colours from deep green, to red, and to blue. In addition, direct white-light emission upon UV excitation can be achieved in the SmxGd1−x-1 system.

Designing antibody-powered DNA nanodevice switches is crucial and fascinating to perform a variety of functions in response to specific antibodies as regulatory inputs, achieving highly sensitive detection by integration with simple amplified methods. In this work, we report a unique DNA-based conformational switch, powered by a targeted anti-digoxin mouse monoclonal antibody (anti-Dig) as a model, to rationally initiate the hybridization chain reaction (HCR) for enzyme-free signal amplification. As a proof-of-concept, both a fluorophore Cy3-labeled reporter hairpin (RH) in the 3' terminus and a single-stranded helper DNA (HS) were individually hybridized with a recognition single-stranded DNA (RS) modified with Dig hapten, while the unpaired loop of RH was hybridized with the exposed 3'-toehold of HS, isothermally self-assembling an intermediate metastable DNA structure. The introduction of target anti-Dig drove the concurrent conjugation with two tethered Dig haptens, powering the directional switch of this DNA structure into a stable conformation. In this case, the unlocked 3'-stem of RH was implemented to unfold the 5'-stem of the BHQ-2-labeled quench hairpin (QH), rationally initiating the HCR between them by the overlapping complementary hybridization. As a result, numerous pairs of Cy3 and BHQ-2 in the formed long double helix were located in spatial proximity. In response to this, the significant quenching of the fluorescence intensity of Cy3 by BHQ-2 was dependent on the variable concentration of anti-Dig, achieving a highly sensitive quantification down to the picomolar level based on a simplified protocol integrated with enzyme-free amplification.

Increasing evidence has shown that the gut microbiota plays an important role in preventing obesity; however, the mechanism by which insoluble dietary fiber (IDF) prevents high-fat diet (HFD)-induced obesity remains unclear. This study aimed to investigate the effect of SIDF on obesity in HFD mice and determine the mechanism by which it prevents obesity through regulating the gut microbiota. Soybean insoluble dietary fiber (SIDF) was used as an intervention in HFD mice for 20 weeks. The results showed that SIDF significantly reduced the body weight (BW), fat index, total cholesterol, triglyceride, and low-density lipoprotein cholesterol while increasing the content of high-density lipoprotein cholesterol in HFD mice. SIDF intervention was also beneficial for the reduction of liver lipid content and fatty droplets in mice. Furthermore, SIDF intervention improved the gut microbiota composition by increasing the relative abundance of potentially beneficial bacteria (such as Lactobacillales [order], Lactobacillus [genus], Lachnospirace_Nk4A136_group [genus]), and reduced the relative abundance of potentially harmful bacteria (such as Lachnospiraceae [family] and Bacteroides_acidifaciens [species]), which correlated with obesity (at least p < 0.05 in all instances). Finally, SIDF was fermented by related beneficial bacteria, which increased the content of the short-chain fatty acids (SCFAs), and promoted the secretion of satiety hormones. In conclusion, SIDF intervention could prevent obesity in HFD mice by modulating the gut microbiota composition. Hence, SIDF may be used as a potential ingredient in functional foods.

Ag-alloyed Cu2ZnSn(S,Se)4 kesterite semiconductors have been attracting considerable attention recently because doping with Ag can suppress the CuZn related anti-site defects, which is the main factor that limits the efficiency of kesterite solar cells. Although the performance of the thin film and the device is enhanced (for example, better crystallinity, fewer deep level defects and longer lifetime of the minority carrier) by doping a small amount of Ag in the CZTS thin film, the density of the defects remains high, and the band alignment of CdS/CZTS is not fully optimized, and the interface carrier concentration is greatly decreased. These phenomena will limit any further improvement in efficiency. In this work, to further increase the performance of the device, the interface of CdS/CZTS for an Ag-alloyed CZTS thin film solar cell was doped with In or Al. Then the properties of the thin film, interface band structure and device performance were investigated. After doping the interface with In or Al, the concentrations of the n-type and p-type carriers at the CdS/CAZTS heterojunction were boosted, and the interface band alignment was optimized, resulting in over 11% efficiency for an Ag-alloyed CZTS (with Al interface doping) thin film solar cell. Moreover, low-cost Al-doped ZnO (AZO) was used to replace indium tin oxide (ITO) as the front electrode after optimization, and more than 10% efficiency of CAZTS device without In was obtained. This study demonstrates the feasibility of controlling the doping of the interface to improve the interface performance of a heterojunction by using a simple spin coating process, and also provided a suitable experimental basis for future low-cost thin film solar cells.

Two POM-based copper coordination polymers constituted by Keggin-type polyoxometalates (POMs), [Cu2 (SiW12O40)2 (Fbtx)3 (H2O)4]n (1) and {[Cu2 (SiW12O40) (Fbtx)2 (H2O)2.75]·4.5H2O}n (2) (Fbtx = 2,3,5,6-tetrafluoro-1,4-bis (1,2,4-triazole-1-ylmethyl)benenze) have been hydrothermally synthesized by the same precursor at different pH values and structurally characterized by single-crystal X-ray diffraction, powder X-ray diffraction, element analyses and IR. Both of them have two-dimensional coordination layers constructed by bidentate SiW12O404− anions and bridging Fbtx ligands, in which complex 1 exhibits a 2D + 2D → 2D interpenetrated network with sql topology, while complex 2 features a binodal 3,5-connected network bearing new topology with a Schlafli symbol of {44;66}{62;10}. Additionally, the thermal stability, fluorescent properties and photocatalytic properties of complexes 1 and 2 have also been investigated. The results indicate that complexes 1 and 2 can serve as recyclable heterogeneous photocatalysts and show good catalytic activity for the degradation of Rhodamine B under UV irradiation.

Vina-ginsenoside R4 (VGN4) is the first example of protopanaxatriol saponin possessing sugar chains located at C-3 and C-20 of aglycone. However, to the best of our knowledge, no report has been published on the neuroprotective effect of VGN4. In the present work, we investigated the neuroprotective effect of VGN4 against 6-hydroxydopamine (6-OHDA)-induced toxicity and its potential mechanism. Pretreatment of PC12 cells with VGN4 attenuated 6-OHDA-induced cell damage and cell apoptosis, which was correlated with the decrease of reactive oxygen species and the increase of antioxidant enzyme activities including superoxide dismutase and catalase. In addition, VGN4 markedly decreased nuclear translation of the nuclear factor-κB and PI3K/Akt/GSK/3β signaling pathway including p85, PDK1, Akt, and GSK-3β. Further studies revealed that PI3K siRNA attenuated the neuroprotective effect of VGN4 on caspase-3 activity. These data indicate that VGN4 might have the potential to be developed as a new neuroprotective functional food.

Yttria-modified silicide (MoSi2-Y2O3) oxidation-resistant coatings with multiple Y2O3 contents were prepared using supersonic atmospheric plasma spraying, and the oxidation resistance was investigated at 1700 °C with static atmosphere. Experimental results indicated that the sprayed MoSi2-Y2O3 coating possessed good compactness, which adhered well to the SiC transition layer. Meanwhile, the Y2O3 addition greatly enhanced the bonding strength of the coating, and extended its service life at 1700 °C. Wherein the MoSi2-20 wt.%Y2O3 coating exhibited the highest adhesive strength and best oxidation resistance with the lowest mass loss among all the coatings. In practice, the Y2O3 changed the microstructures of formed oxide glass scale during oxidation, and then modified the oxidation resistance of the coating. The action mechanism of Y2O3 on the oxidation behavior of MoSi2-Y2O3 coating was analyzed.

Adipocyte differentiation involves a series of highly synergistic processes, including clone amplification, proliferation arrest, and terminal differentiation. However, the mechanisms that control these different steps remain unclear. Emerging studies support that miRNAs play an important role in regulating adipogenesis. In this study, we found that the expression of miR-345-5p decreased during adipogenic differentiation, and overexpression of miR-345-5p reduced lipid accumulation in adipocytes and the expression of adipocyte related genes essential to lipogenic transcription, fatty acid synthesis and fatty acid transport. In addition, miR-345-5p directly targeted the 3'UTR of vascular endothelial growth factor B, and miR-345-5p mimic inhibited the expression of vascular endothelial growth factor B at both mRNA and protein levels. In conclusion, our results demonstrate that miR-345-5p inhibits adipocyte differentiation via targeting vascular endothelial growth factor B.

Dark or weak-emissive DNA-harbored silver nanoclusters (AgNCs) can be remarkably lighted up when approaching to guanine bases. The resultant bright AgNCs acting as a fluorescent reporter are fascinating in biosensing. To explore the applicable guanine-enhanced emission of AgNCs for biosensing microRNA-155 (miR-155) as a model, here we designed a unique stem-loop hairpin beacon (HB) encoding with an miR-155-recognizable sequence and a AgNCs-nucleable template, as well as a hairpin helper tethering a partially locked guanine-rich (15-nt) tail (G15H), while two identical cytosine-rich segments were inserted in HB and G15H to merge for folding/unfolding of i-motif at changed pHs. Initially, the intact clusters populated in HB (HB/AgNCs) were almost nonfluorescent in a buffer (pH 7.0). Then, miR-155 was introduced to trigger a repeated hairpin assembly of HB and G15H by competitive strand displacement reactions at decreased pH 5.0 within 10 min, consequently generating numerous duplex DNA constructs (DDCs). With the resultant template of pH-responsive i-motifs incorporated in DDCs, their folding at pH 5.0 brought the proximity of unlocked G15 overhang to the clusters in a crowded environment, remarkably lighting up the red-emitting fluorescence of HB/AgNCs (λem = 628 ± 5 nm) for amplified signal readout. About 3.5-fold enhancement of quantum yield was achievable using different variants of i-motif length and G15 position. Simply by adding OH-, the configuration fluctuation of i-motifs was implemented for switchable fluorescence biosensing to variable miR-155. Based on a one-step amplification and signaling scheme, this subtle strategy was rapid, low-cost, and specific for miR-155 with high sensitivity down to 67 pM.

Nuclear receptors (NRs) are key regulators of energy homeostasis, body development, and sexual reproduction. Xenobiotics binding to NRs may disrupt natural hormonal systems and induce undesired adverse effects in the body. However, many chemicals of concerns have limited or no experimental data on their potential or lack-of-potential endocrine-disrupting effects. Here, we propose a virtual screening method based on molecular docking for predicting potential endocrine-disrupting chemicals (EDCs) that bind to NRs. For 12 NRs, we systematically analyzed how multiple crystal structures can be used to distinguish actives and inactives found in previous high-throughput experiments. Our method is based on (i) consensus docking scores from multiple structures at a single functional state (agonist-bound or antagonist-bound), (ii) multiple functional states (agonist-bound and antagonist-bound), and (iii) multiple pockets (orthosteric site and alternative sites) of these NRs. We found that the consensus enrichment from multiple structures is better than or comparable to the best enrichment from a single structure. The discriminating power of this consensus strategy was further enhanced by a chemical similarity-weighted scoring scheme, yielding better or comparable enrichment for all studied NRs. Applying this optimized method, we screened 252 fatty acids against peroxisome proliferator-activated receptor gamma (PPARγ) and successfully identified 3 previously unknown fatty acids with Kd = 100–250 μM including two furan fatty acids: furannonanoic acid (FNA) and furanundecanoic acid (FUA), and one cyclopropane fatty acid: phytomonic acid (PTA). These results suggested that the proposed method can be used to rapidly screen and prioritize potential EDCs for further experimental evaluations. Electronic supplementary material The online version of this article (10.1007/s00204-020-02897-x) contains supplementary material, which is available to authorized users.

Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown. Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 (EPAS1), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques. Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug. Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1, thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel.

Modern advanced photonic integrated circuits require dense integration of high-speed electro-optic functional elements on a compact chip that consumes only moderate power. Energy efficiency, operation speed, and device dimension are thus crucial metrics underlying almost all current developments of photonic signal processing units. Recently, thin-film lithium niobate (LN) emerges as a promising platform for photonic integrated circuits. Here, we make an important step towards miniaturizing functional components on this platform, reporting high-speed LN electro-optic modulators, based upon photonic crystal nanobeam resonators. The devices exhibit a significant tuning efficiency up to 1.98 GHz V−1, a broad modulation bandwidth of 17.5 GHz, while with a tiny electro-optic modal volume of only 0.58 μm3. The modulators enable efficient electro-optic driving of high-Q photonic cavity modes in both adiabatic and non-adiabatic regimes, and allow us to achieve electro-optic switching at 11 Gb s−1 with a bit-switching energy as low as 22 fJ. The demonstration of energy efficient and high-speed electro-optic modulation at the wavelength scale paves a crucial foundation for realizing large-scale LN photonic integrated circuits that are of immense importance for broad applications in data communication, microwave photonics, and quantum photonics., Lithium niobate (LN) devices are promising for future photonic integrated circuits. Here, the authors demonstrate an electro-optic LN modulator with a very small modal volume based on photonic crystal resonator architecture.

In this study, we present the use of compositionally and structurally well-defined, oxide-supported nanoparticle Ni + Ga intermetallic compound (IMC) catalysts in the wet reforming of propane. The ...

Microwave-assisted hydrothermal reaction of 2-fluoro-3,5,6-tri(1H-1,2,4-triazol-1-yl)-1,4-benzenedicarbonitrile (L1) with silver(I) nitrate yields a coordination polymer [Ag3(L2)2(NO3)] n (1), in which the L2 ligand (HL2 = 2-hydroxy-3,5,6-tri(1H-1,2,4-triazol-1-yl)terephthalonitrile) is obtained by in situ ligand transformation from the L1 precursor. HL2 monohydrate has also been isolated by the microwave-mediated hydrolysis of L1 and structurally characterized. Single-crystal X-ray diffraction reveals that HL2 monohydrate comprises a zwitterionic HL2 moiety, while complex 1 displays an infinite L2-bridged double-chain structure. Given that the HL2 molecule has a large conjugated π system, complex 1 exhibits strong blue luminescence in the solid state at room temperature.

Herein, a facile intramolecular cyclization of 2-arylamino phenyl ketones is established to supersede the traditional high-temperature, strongly acidic conditions and achieve 9-substituted acridines, by virtue of the combination of 2,2,2-trifluoroethanol and tert-butyl bromide. This protocol can be merged well with the preceding Cu-catalyzed intermolecular Chan-Evans-Lam cross-coupling reactions, therefore enabling pot-economic modular synthesis of 9-substituted acridines from readily available 2-amino phenyl ketones and aryl boronic acids at room temperature.

The storage root of alligatorweed [Alternanthera philoxeroides(Mart.) Griseb.] growing in terrestrial habitats is an important metamorphic organ for its propagation, overwintering, and spread. However, the regulatory mechanism adventitious root expansion to form storage roots is still unclear. To reveal the changes accompanying the root-swelling process, we quantified sugar, soluble protein, and phytohormone content in adventitious and storage roots. Results demonstrated that sucrose, fructose, and soluble protein increased in storage roots, whereas abscisic acid (ABA), indoleacetic acid (IAA), brassinosteroid (BR), gibberellin, jasmonic acid, and cytokinin (trans-zeatin [tZ] and isopentenyladenine [iP] and the corresponding ribosidestZR and iPR).tZ-type (tZR andtZ) content decreased, suggesting the involvement of sugars and hormones in the formation of storage roots. To further reveal the molecular basis ofA.philoxeroides’s ability to form storage roots and provide candidate genes for molecular function analyses, we assembled a de novo transcriptome ofA.philoxeroidesbased on four sets of RNA-sequencing data. According to functional annotation and expression profiling, 42 unigenes involved in sucrose synthesis and hydrolysis were identified, in addition to 70, 58, and 78 unigenes in ABA, BR, and IAA signal transduction, respectively. The quantitative reverse transcriptase polymerase chain reaction analysis revealed 21 unigenes involved in sugar metabolism and hormone signal transduction were differentially expressed during the formation of storage roots. These results revealed metabolic changes during the formation of storage roots and provide candidate genes involved in sugar and phytohormone metabolism inA. philoxeroides.

Rare earths with unique electronic structure and properties have incomparable advantages for modifying the comprehensive performance of silicide materials. In this study, MoSi2-based composite coatings with different rare-earth Yb2O3 contents were prepared using supersonic atmospheric plasma spraying, and their microstructural features and oxidation behavior at 1700 °C were investigated systematically. Results showed that the sprayed MoSi2-Yb2O3 composite coating possessed the dense structure without visible defects and tightly adhered to the SiC transition layer. During oxidation at 1700 °C, all the samples exhibited an explicit linear oxidation mode, in which the MoSi2-10 wt%Yb2O3 coating qualified the optimal oxidation resistance with the lowest specific mass loss relative to other coatings. It was natural to consider that the Yb2O3 dopant changed the microstructural aspects of the formed oxide scale upon oxidation, and then affecting the oxidation behavior of the applied coating. Moderate doping of Yb2O3 stabilized the Si–O covalent bonds in SiO2 network, leading to the enhanced viscosity of oxide glass scale, thereby delaying the effective delivery of oxygen molecules as well as the oxidation degradation of the coating.

Coal-fired power plant is the largest anthropogenic mercury source. Active carbon injection technique has been widely used to control the mercury emissions. However, high operation cost limits its development and it is necessary to find other potential mercury sorbents. In this study, raw semi-coke and a series of novel cerium (Ce) modified semi-cokes were synthesized and utilized for removing elemental mercury (Hg0) from simulated flue gas. It is noteworthy that the efficiencies were tested without hydrogen chloride (HCl) in order to evaluate the sorbents efficacy for low-chlorine (Cl) coal. The results show that the modified sorbents exhibited the best performance at 150 °C. The performance of sorbent could be reinforced due to the existence of oxygen (O2), nitric oxide (NO) and HCl. The adverse effect caused by sulfur dioxide (SO2) reduced dramatically after Ce modification. The negative impact of ammonia (NH3) on Hg0 removal in this study could be neglected owing to the tiny concentration of NH3. Raw semi-coke provided sufficient carbon content, which is favorable to mercury adsorption. As Ce loading increased, the carbon structure changed and the crystal of cerium oxide was formed in the modified semi-coke. The mass fraction of cerium oxide on the sorbent was over 4.4% when the concentration of Ce modification solution was higher than 0.2 mol L−1. The redox reaction activity and the oxygen storage ability of Ce3+/Ce4+ gave a huge boost to the performance of modified semi-coke. The addition of Ce also had an impact on the proportion of oxygen species.

The pleiotropic transcription factor nuclear factor-kappa B (NF-κB) has important functions in viral resistance. In the present study, we isolated a p65 subunit of NF-κB cDNA from Pelteobagrus vachellii (termed Pvp65) and characterized it. The full-length p65 cDNA comprised 3651 bp, including a 148-bp 5'-untranslated region (UTR), a 106-bp 3'-UTR, and an open reading frame encoding a 1067-amino acid putative protein. The protein sequence comprised a DNA binding motif, a Rel-homology domain, a Rel protein signature, a putative transcription activation domain, a nuclear localization signal, and a transcription initiation factor IIA domain. The expression of Pvp65 displayed a daily rhythm, with an acrophase at approximately at 15:32 h in the liver, 11:34 h in the spleen, and 16:45 h in the head kidney. In addition, infection with Aeromonas hydrophila caused Pvp65 expression to increase significantly (P 0.05), and peaking at 12 h post infection in the spleen, at 24 in the head kidney, and at 12 h in the liver. Thus, NF-κB expression might be under light/dark cycle control in P. vachellii, and may be involved in the immune response to A. hydrophila.

Rare earth oxides usually play an active role in modifying the microstructure and oxidation resistance of silicide coatings, but its modification mechanism has not yet been clarified. In this work, molybdenum silicide (MoSi2) coating with different contents of ytterbium oxide (Yb2O3) was fabricated using supersonic atmospheric plasma spraying, and its microstructural evolution and oxidation behavior were investigated. Experimental results shown that the morphological characteristics of produced SiO2-rich glass scale varied with the doping of Yb2O3, which noticeably affected the oxidation resistance of sprayed MoSi2-Yb2O3 coatings. All coated specimens exhibited a parabolic oxidation behavior, wherein the MoSi2-10 wt%Yb2O3 coating possessed the smallest parabolic constant and the lowest specific mass loss with 100 h oxidation at 1500 °C due to the absence of SiC-depleted region and the formation of continuous multicomponent compound scale. Given this, Yb2O3 additive with proper concentration not only guaranteed the sufficient filling of open spaces in SiO2 network by Yb3+ cations, but also strengthened the Si–O bonds to increasing the viscosity of SiO2 glass, thereby delaying the effective delivery of reactive oxygen species inwardly.

To date, the iron-catalyzed construction of C–heteroatom bonds has been less developed due to the difficulty of transmetalation with heteroatom anions and the sluggish reductive elimination. Herein...

Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development., Whole-cell catalyst-based hydroxytyrosol production is low. Here, the authors increase the efficiency of its production in E. coli by de-bottlenecking two enzymatic steps catalyzed by monooxygenase and tyramine oxidase using structure-based enzyme redesign or in vivo-directed evolution with the aid of a newly developed biosensor.

The solubility of N-acetyl-l-leucine in 12 mono organic solvents (methanol, ethanol, n-propanol, 2-propanol, 1-butanol, isobutanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, acetone...

The solubility of ceftiofur sodium trihydrate (CST) in binary solvent mixtures of water + acetonitrile, water + ethanol, water + n-propanol, and water + iso-propanol at temperatures from 273.15 to 313.15 K (P = 0.1 MPa) was measured by a laser dynamic method. The experimental results show that the solubility is positively correlated with temperature. In the four binary solvent systems, the solubility value of CST initially increases first and then decreases with increasing organic solvent composition. The maximum solubility values occur in the molar content of organic solvent of about 0.5 for water + acetonitrile, 0.5 for water + ethanol, 0.4 for water + n-propanol, and 0.4 for water + iso-propanol. The accuracy of experimental results was examined by the Apelblat model, the Van’t-JA model, and the Apel-JA model, and the Apelblat model shows the best fitting performance.

Accumulating evidence has indicated that microRNAs can regulate downstream signaling pathways and play an important role in various tumors. In this study, we found that miR-223-3p was differentially expressed in 40 paired gastric cancer tissues and adjacent tissues and that miR-223-3p was positively correlated with tumor invasion depth and lymph node metastasis. Luciferase reporter assay confirmed that Arid1a was the target gene of miR-223-3p. Functional assays showed that miR-223-3p promoted the proliferation and invasion of gastric cancer cells by regulating the expression of Arid1a. We also confirmed that miR-223-3p regulated the growth of gastric cancer cells in vivo, while an antagomir against miR-223-3p significantly inhibited tumor growth. In conclusion, our results demonstrated that miR-223-3p inhibits gastric cancer cell progression by decreasing the expression of Arid1a. Therefore, miR-223-3p may act as a potential therapeutic target for patients with gastric cancer.

In this paper, a series of shape-memory poly(arylene ether ketone)s (PAKEs) with various flexible groups (i.e., carbolic bonds, ether, and ketone linkages) and entangled crystalline polymeric structures were synthesized by combining different bisphenol monomer (bisphenol A monomer and methyl hydroquinone monomer) proportions with a 4,4′-difluorobenzophenone monomer. The flexible parts and the entangled parts acted as a reversible phase and permanent phase, respectively. The prepared PAEK films exhibited excellent heat-triggered shape-memory behaviors with tunable glass transition temperatures (Tg) from 116 °C to 140.5 °C including an extremely high fixity ratio (over 98%), high recovery ratio (over 92%), and fast recovery rate (within 7.0 s). As increasing the content of the methyl hydroquinone monomer in the structural unit, the recovery ratio showed a downward trend, whereas the recovery time increased gradually. In addition, the electric-triggered shape-memory effect of the PAEK films was achieved via the introduction of carbon nanotubes (CNTs). Upon applying a voltage of 25 V, the recovery ratios of the composite films containing 10 wt% and 15 wt% CNTs were all over 80% (of 83.0% and 87.6%, respectively), indicating a great electric-triggered shape-memory behavior. The recovery ratio increased and the triggered voltage decreased as increasing the content of CNTs. The heat and electric dual-triggered shape-memory PAEK composites could be important smart materials possessing wide application prospects.

Lithium metal is a potential candidate for next-generation anode materials. However, the practical application of a lithium metal anode has been hindered by uncontrolled dendrite formation. Herein, a cost-effective single lithium ion conducting polymer electrolyte membrane based on a highly porous lithium sulfonated polyether ether ketone electrospun nanofiber membrane (es-LiSPCE) is designed to serve as both a separator and a lithium ion conductor. Impregnation of the ethylene carbonate (EC)/dimethyl carbonate (DMC) (v/v = 1 : 1) solvent mixture and 1 M LiFP6 in EC/PC (v/v = 1 : 1) yields gel pure es-LiSPCE and es-LiSPCE/1 M LiFP6 in an EC/PC (v/v = 1 : 1) membrane, respectively, which display high ionic conductivity, low interfacial compatibility and a high lithium ion transference number. Combined scanning electron microscopy (SEM) images and the long-term stripping/plating cycling test of lithium foil confirm that such a membrane is greatly favorable for inhibiting the formation of a concentration gradient and thus suppressing lithium dendrite growth. In addition, the fully aromatic polyether ether ketone backbone enables high thermal dimensional stability and high polarity and high polarity enables fast electrolyte wetting of the es-LiSPCE membrane. Notably, Li/LiFePO4 cells fabricated using es-LiSPCE membranes demonstrate promising rate capacity at 6C, and excellent electrochemical stability for 1500 cycles even at 6C. Therefore, it is believed that such an electrolyte can serve as an alternative to conventional polyolefin-based separators for high energy density lithium metal batteries.

By utilizing a flexible fluorinated bis(triazole) ligand 1,4-bis(1,2,4-triazole-1-ylmethyl)-2,3,5,6-tetrafluorobenzene (Fbtx), a thermally and chemically stable cobalt(II)-containing tungstovanadate-based metal–organic framework (MOF) {[Co3(Fbtx)5(V2W18O62)(H2O)2]·26H2O}n (denoted as CZU-5) was synthesized and structurally characterized. The X-ray structural analysis revealed that CZU-5 features a three-dimensional (3-D) self-penetrated α-polonium cubic structure, which results from a 3-D 4-fold interpenetrated diamondoid [Co(Fbtx)]n network connected by the Wells–Dawson-type tungstovanadate clusters. Unexpectedly, the introduction of vanadium atoms as heteroatoms into the Dawson-type anion in polyoxometalate (POM)-based coordination polymers has not been reported to date. For the first time, the POM-based material was demonstrated to be an effective catalyst for the solvent-free ring-opening polymerization of e-caprolactone. Moreover, the CZU-5 catalyst could be recycled up to five times with the retention of both catalytic activity and crystal structure.

By using La(NO3)3•6H2O, Ca(NO3)2•4H2O, and Mn(CH3COO)2•4H2O as starting raw materials together with methanol, three kinds of La0.67Ca0.33MnO3 (LCMO) solutions, denoted as LCMO–BzAc, LCMO–AcAc, and LCMO–BPY, respectively, were obtained. The samples were fabricated via the photosensitive solution method with benzoylacetone (BzAc), acetylacetone (AcAc), and 2, 2′-bipyridine (BPY) as chelating reagents. The chelation mechanism of the metal ions was investigated via ultraviolet spectroscopy. The photosensitive compounds were decomposed after UV exposure and their products reduced the solubility of the LCMO gel films in organic solvents. The patterned LCMO thin films were then fabricated by using the self-photosensitive properties of their gel films. Through the mask micromachining process, the LCMO micropatterns prepared by using the LCMO–BzAc solution exhibited the highest quality. Moreover, they also presented good performance when the mask-free method was employed. The magnetic properties of the micropatterned LCMO films were investigated in detail and the results revealed that the micropatterning did not influence their saturation magnetization.

A novel composite membrane with membrane pores loading acrylic acid microgels coated by Fe–Pd bimetallic nanoparticles (NPs) was prepared for the dechlorination of trichloroethene (TCE) in water. This membrane was prepared by firstly immobilizing acrylic acid microgels in poly (vinylidene fluoride) (PVDF) membrane pores and then in-situ synthesis of Fe–Pd bimetallic nanoparticles (NPs). The Fe–Pd NPs coupled with the porous membranes enabled dechlorination to be conducted in a cross-flow model including a penetrative flow and a tangential flow. In such a model, a large number of dechlorination occurred in penetrative flow fluid while no dechlorination occurred in tangential flow fluid. Thus, products and reactants are always timely isolated in the cross-flow dechlorination process. The composite membrane prevents Fe–Pd NPs from contamination because its nanosize surface pores stop colloids and bovine serum albumin (BSA) from entering into the membrane interior. However, these small surfaces pores cannot slow the diffusion of reactants into membrane pores, and thus make the as-formed composite membrane also show a fast dechlorination rate in a batch reaction. All in all, TCE dechlorination by the composite membrane shows many advantages including the fast dechlorination rate, the convenient operation, the timely isolation of products from reactants, and the ignorable extra steps for separation of metal NPs.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD–PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD–PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO(3)), bicarbonate in superior vena cava (svcHCO(3)), and the partial pressure of dissolved CO(2) gas in radial artery (aPCO(2)) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P

Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3′UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.

Skin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR‐411‐3p in bleomycin (BLM)‐induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real‐time quantitative polymerase chain reaction assess the expression levels of miR‐411‐3p, collagen (COLI) and transforming growth factor (TGF)‐β/Smad ubiquitin regulatory factor (Smurf)‐2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR‐411‐3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR‐411‐3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR‐411‐3p expression was decreased in bleomycin (BLM)‐induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)‐β signalling and collagen production. Overexpression of miR‐411‐3p inhibited the expression of collagen, F‐actin and the TGF‐β/Smad signalling pathway factors in BLM‐induced skin fibrosis and fibroblasts. In addition, miR‐411‐3p inhibited the target Smad ubiquitin regulatory factor (Smurf)‐2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF‐β/Smad signalling pathway. We demonstrated that miR‐411‐3p exerts antifibrotic effects by inhibiting the TGF‐β/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.

The spleen is a separate organ of the teleost, playing an essential role in immune reactions. The morphology of the spleen is different from the fish species. Little knowledge about the spleen structure and the blood splenic barrier (BSB) in Nile tilapia has been reported. To address this issue, we studied the histology of the spleen and the BSB in healthy Nile tilapia. The morphology of the spleen was observed, then H&amp, E staining, modified Jame’s staining, and ultrastructural techniques were performed to portion the spleen into three subregions and analyze the location of components and fibers. Thereafter, vital staining of Nile tilapia with Trypan blue was conducted to elucidate the composition and function of BSB. Histologically, the spleen could be divided into three subregions (inner, middle, and outer). The venules, clumps of lymphocytes, and vessels were separately characterized features of the outer, middle, and inner layers. Post injection, Trypan blue was intercepted in the endotheliocytes of ellipsoids in the middle layer (i.p.) or was deposited to the reticular fibers surrounding the ellipsoids (i.v.). Additionally, the amount of Trypan blue was shown to be positively correlated to that of the Acid phosphatase expressed. In conclusion, the spleen could be portioned into three subregions, and the BSB lay in the middle layer, composed of the cuboidal-shaped endotheliocytes and the surrounding reticular fibers of the ellipsoid capillaries. The present study enriched the research of immune tissues and system in tilapia and provided reference for the study of spleen in other fish species.

The influences of on-resistances and parasitic elements on the static current sharing of N-paralleled discrete silicon carbide (SiC) MOSFETs are analyzed in this paper. First of all, the limitation of self-balancing effect of MOSFETs caused by the positive temperature dependent on-resistance is quantitatively analyzed. From a statistical analysis, the current sharing distribution according to the spread of on-resistances is presented, which helps to screen the proper devices based on the current sharing requirement. Furthermore, a general circuit model is proposed to analyze the effect of inevitable circuit parasitic elements on current sharing with a given current slew rate. With the recursive circuit model, current imbalance contributed by parasitic resistances and inductances can be separately calculated, which can be used to guide the hardware design to improve current sharing in a real converter. The theoretical analysis is verified by experimental results.