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The assembly of biomacromole particles with artificial solid matrixes to fabricate hybrid composites has been demonstrated as an efficient strategy to promote both components’ applications. Elaborating matrixes as well as appropriate assembly method is essential for optimal performances of the obtained natural-artificial composites. Herein, we fabricated the Cyt c@COF-42-B microcapsule through a sacrificial templating method and researched their adjustable biocatalysis by precisely adjusting the microenvironments of these assembled enzyme@COF particles. As a result, the hydrophobicity and mass transfer of the COF microcapsule can be controlled by modifying the different amounts of PEG moieties, thus improving the composite's bioactivity. We found that compared with pristine Cyt c@COF-42-B without PEG, the Cyt c@COF-42-B-PEG exhibited a ∼2.2 times higher activity. This study provides a significant step toward designing customizable functional natural-artificial composites for enhanced biomacromolecule's activity.

Changes in intestinal flora affect the health and cause metabolic diseases of the host. The extent to which the impact of different changes in intestinal flora would have on the metabolism of an individual has not been reported. This study aims to investigate the effect of different changes in intestinal flora on the metabolism of Sprague–Dawley (SD) normal rats’ individuals. Forty-eight SD rats were randomly divided into 6 groups (8 rats per group), which were treated with normal saline, probiotics, nonpathogenic Escherichia coli, Salmonella enteritidis, gentamicin, and magnesium sulfate, respectively. After 7 days, the ileum of each group of rats was collected and real-time polymerase chain reaction was used to analyze the composition of intestinal flora. And gas chromatography/mass spectrometry (GC/MS) was used to analyze plasma metabolic profile. The results revealed that the decrease in alanine content in the probiotics group was statistically significant, while the alanine content in the nonpathogenic Escherichia group increased significantly. Alanine, leucine, isoleucine, and serine decreased significantly in the Salmonella group. Proline and butyric acid decreased significantly in the gentamicin group. The principal component analysis showed significant differences in the Salmonella group compared with other test groups. Overall, the most significant metabolic changes were observed in SD rats in the Salmonella group, while a great similarity was observed in the probiotics, Escherichia group, and gentamicin groups compared with the normal group. Changes in intestinal flora had a certain impact on the metabolism in SD rats, especially on amino acid levels.

Single-atom catalysts (SACs) with metal–nitrogen (M–N) moiety are effective in boosting the redox kinetics of lithium–sulfur (Li–S) batteries. However, the precise preparation of SACs with controll...

A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4-dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

The classic neurotransmitter γ-aminobutyric acid (GABA) has been shown to shape the activation and function of immune cells. There are four high-affinity GABA transporters (GATs, including GAT-1, GAT-2, GAT-3, and GAT-4) responsible for the transmembrane transport of GABA in mice. To explore the effect of GAT-2 on type 1 helper T (Th1) cells, naive CD4+ T cells were isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice and cultured for Th1 cell differentiation, and then, metabolomics analysis of Th1 cells was performed via gas chromatography coupled to time-of-flight mass spectrometry added with multivariate analyses. Based on the variable importance projection value > 1 and P < 0.05, a total of nine differentially expressed metabolites (DEMs) were identified between WT and KO. Then, DEMs were mapped to the KEGG database, and five metabolic pathways were significantly enriched, including the cysteine and methionine metabolism, the riboflavin metabolism, the purine metabolism, the glycerolipid metabolism, and the glycerophospholipid metabolism. Collectively, our metabolomics analysis revealed that deficiency of GAT-2 influenced the metabolomics profile of Th1 cells, which will provide insights into T cell response to GAT-2 deficiency in mice. Data are available via MetaboLights with identifier MTBLS3358.

Layered O3 type oxides exhibit promising prospects as high-performance cathodes for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. Nevertheless, the intrinsic surface composition and bulk structure degradation upon cycling presents a huge obstacle to stable sodium-ion storage/transportation. Besides, the effective surface decoration on layered O3 oxides is still challenging through conventional wet chemical route owing to their extraordinarily high surface sensitivities. Herein, a typical O3 type layered oxide of NaNi0.5Mn0.5O2 (NNMO) was selected and successfully encapsulated by precisely controlled Al2O3 layers via atomic layer deposition (ALD) technology. With the optimally controlled Al2O3 thickness of 3 nm, the surface regulated NNMO delivers a highly reversible capacity of 73.6 mA h g-1, with a significantly improved capacity retention of 68.0% after 300 cycles at 0.5 C, and a superior rate capability of 65.8 mA h g-1 at 10 C. Further air sensitivity tests demonstrate that the protective layer could effectively mitigate the generation of sodium-based impurities on NNMO, and reduce the surface sensitivities. Both chemical and electrochemical aging tests confirm the contribution of Al2O3 coating layer in alleviating ion dissolution as well as stabilizing the structure and morphology of NNMO. Based on regulating the surface of O3 type layered oxides utilizing ALD technique, this work supplies an effective and facile strategy to overcome the challenges from fast structure degradation and electrochemical property decay, which not only highlights the significance and effectiveness of surface engineering in secondary batteries, but also sheds light on accurate interface construction and regulation for active electrode materials, particularly for those sensitive to ambient atmosphere.

Graphical abstract, Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes severe infection in humans characterized by an acute febrile illness with thrombocytopenia and hemorrhagic complications, and a mortality rate of up to 30%. Understanding on virus-host protein interactions may facilitate the identification of druggable antiviral targets. Herein, we utilized liquid chromatography-tandem mass spectrometry to characterize the SFTSV interactome in human embryonic kidney-derived permanent culture (HEK-293T) cells. We identified 445 host proteins that co-precipitated with the viral glycoprotein N, glycoprotein C, nucleoprotein, or nonstructural protein. A network of SFTSV-host protein interactions based on reduced viral fitness affected upon host factor down-regulation was then generated. Screening of the DrugBank database revealed numerous drug compounds that inhibited the prioritized host factors in this SFTSV interactome. Among these drug compounds, the clinically approved artenimol (an antimalarial) and omacetaxine mepesuccinate (a cephalotaxine) were found to exhibit anti-SFTSV activity in vitro. The higher selectivity of artenimol (71.83) than omacetaxine mepesuccinate (8.00) highlights artenimol’s potential for further antiviral development. Mechanistic evaluation showed that artenimol interfered with the interaction between the SFTSV nucleoprotein and the host glucose-6-phosphate isomerase (GPI), and that omacetaxine mepesuccinate interfered with the interaction between the viral nucleoprotein with the host ribosomal protein L3 (RPL3). In summary, the novel interactomic data in this study revealed the virus-host protein interactions in SFTSV infection and facilitated the discovery of potential anti-SFTSV treatments.

Background Pancreatic cancer is a highly malignant tumor of the gastrointestinal system whose emerging resistance to chemotherapy has necessitated the development of novel antitumor treatments. Scoparone, a traditional Chinese medicine monomer with a wide range of pharmacological properties, has attracted considerable attention for its antitumor activity. Aim To explore the potential antitumor effect of scoparone on pancreatic cancer and the possible molecular mechanism of action. Methods The target genes of scoparone were determined using both the bioinformatics and multiplatform analyses. The effect of scoparone on pancreatic cancer cell proliferation, migration, invasion, cell cycle, and apoptosis was detected in vitro. The expression of hub genes was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the molecular mechanism was analyzed using Western blot. The in vivo effect of scoparone on pancreatic cancer cell proliferation was detected using a xenograft tumor model in nude mice as well as immunohistochemistry. Results The hub genes involved in the suppression of pancreatic cancer by scoparone were obtained by network bioinformatics analyses using publicly available databases and platforms, including SwissTargetPrediction, STITCH, GeneCards, CTD, STRING, WebGestalt, Cytoscape, and Gepia; AKT1 was confirmed using qRT-PCR to be the hub gene. Cell Counting Kit-8 assay revealed that the viability of Capan-2 and SW1990 cells was significantly reduced by scoparone treatment exhibiting IC50 values of 225.2 μmol/L and 209.1 μmol/L, respectively. Wound healing and transwell assays showed that scoparone inhibited the migration and invasion of pancreatic cancer cells. Additionally, flow cytometry confirmed that scoparone caused cell cycle arrest and induced apoptosis. Scoparone also increased the expression levels of Bax and cleaved caspase-3, decreased the levels of MMP9 and Bcl-2, and suppressed the phosphorylation of Akt without affecting total PI3K and Akt. Moreover, compared with the control group, xenograft tumors, in the 200 μmol/L scoparone treatment group, were smaller in volume and lighter in weight, and the percentages of Ki65- and PCNA-positive cells were decreased. Conclusion Our findings indicate that scoparone inhibits pancreatic cancer cell proliferation in vitro and in vivo, inhibits migration and invasion, and induces cycle arrest and apoptosis in vitro through the PI3K/Akt signaling pathway.

Currently available therapies for hepatocellular carcinoma (HCC), with a high morbidity and high mortality, are only marginally effective and with sharp adverse side effects, which makes it compulsory to explore novel and more effective anticancer molecules. Chinese medicinal herbs exhibited prominent anticancer effects and were applied to supplement clinical cancer treatment. Here, we reported a compound, trilobolide-6-O-isobutyrate (TBB), isolated from the flowers of Wedelia trilobata with a markedly cytotoxic effect on HCC cells. We found that TBB time- and dose-dependently inhibited HCC cells' growth and colony formation in vitro. Moreover, TBB induced cell cycle arrest at the G2/M phase, mitochondrial caspase-dependent apoptosis, and suppressed migration and invasion, as well as the glycolysis of HCC cells. Mechanistically, our data indicated that TBB inhibited the STAT3 pathway activation by directly interacting with the TYR 640/657 sites of the STAT3 protein and decreasing the level of p-STAT3. TBB also regulated the expression of PCNA, Ki67, Cyclin B1, Cyclin E, Bax, Bcl2, MMP2/9, and PGK1 through the inhibition of the IL-6/STAT3 signaling pathway. Lastly, we confirmed that TBB effectively eliminated tumor growth without causing overt toxicity to healthy tissues in the xenograft tumor model. The exploration of anticancer activity and the underlying mechanism of TBB suggested its usage as a promising chemotherapeutic agent for HCC.

Berbamine is a bisbenzylisoquinoline alkaloid extracted from Berberis poiretii of Berberis of Berberidaceae. It has been reported that it can significantly inhibit the proliferation of a variety of malignant tumor cells, including liver cancer. However, the effect of berbamine on the invasion and metastasis of liver cancer has not been reported. The present study demonstrated that berbamine inhibited the migration and invasion of SMMC-7721 cells in a concentration-dependent manner and obviously increased the gap junction function and the expression of Cx32 in SMMC-7721 cells compared with control group. However, after silencing Cx32, berbamine had no significant effect on cell invasion and metastasis. Before silencing Cx32, the expression of PI3K and P-AKT were decreased after berbamine treated on SMMC-7721 cells for 24 h. After silencing Cx32, the expression of PI3K and P-AKT were increased in SMMC-7721 cells. The expression of PI3K and P-AKT had no significant effect after berbamine treated on SMMC-7721 cells for 24 h with silencing Cx32. In conclusion, the results of the present study suggest that berbamine could inhibit the SMMC-7721 cell migration and invasion, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway by enhancing the expression of Cx32.

Exploration of novel material platforms to protect biological preservatives and realize intelligent regulation during fermentation is of great significance in industry. Herein, we established an intelligent responsive platform by introducing antimicrobial biomolecules (nisin) into rationally designed covalent organic frameworks (COFs), resulting in a new type of "smart formulation", which could responsively inhibit microbial contamination and ensure the orderly progression of the fermentation process. The encapsulated biomolecules retained their activity while exhibiting enhanced stability and pH-responsive releasing process (100% bacteriostatic efficiency at a pH of 3), which can ingeniously adapt to the environmental variation during the fermentation process and smartly fulfill the regulation needs. Moreover, the nisin@COF composites would not affect the fermentation strains. This study will pave a new avenue for the preparation of highly efficient and intelligent antimicrobial agents for the regulation of the fermentation process and play valuable roles in the drive toward green and sustainable biomanufacturing.

MicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3′ untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.

The Pt/(Fe, Mn/Co)-BTC catalysts were fabricated by a facile ultrasonic impregnation assisted hydrothermal polyol reduction method using first MIL-100(Fe, Mn/Co) MOFs as supports and tested for selective hydrogenation of furfural (FAL) to furfuryl alcohol (FOL). Various characterizations including XRD, TG, FT-IR, N2 physical adsorption, ICP-OES, SEM, TEM and XPS were applied for exploring structure changes and surface properties of the catalysts. Over 98% conversion of FAL and 99% selectivity to FOL were achieved over Pt/(Fe, Mn)-BTC and Pt/(Fe, Co)-BTC, moreover, Pt/(Fe, Co)-BTC showed higher turnover frequency (TOF) of 1,044 h−1 and better cycle stability, which are better than other catalysts prepared by using H2, NaBH4, and formaldehyde as reductants. Overall, the formation of highly dispersed small-sized Pt NPs (about 1.7 nm) with much higher content of surface Pt0 on the catalysts is the key of excellent hydrogenation activity due to the strong interaction between Pt NPs and the bimetallic supports.

The combination of graphene oxide (GO) and iron oxide (Fe2O3) may induce property enforcement and application extension. Herein, GO/Fe2O3 nanocomposites were synthesized via the vacuum-freeze-drying method and used for the thermal decomposition of ammonium perchlorate (AP). A series of characterization techniques were applied to elucidate the as-obtained nanomaterial's physicochemical properties. These results show that the treated GO is consistent with the pristine GO after the freeze-drying treatment. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses show that iron oxide nanoparticles are anchored on and between the GO sheets. The catalytical effect investigation on AP with different Fe2O3: GO ratios indicates that the high-temperature decomposition temperature of AP could be decreased by a temperature as high as 77 °C compared to pure AP accompanied by 3 wt % GO/Fe2O3 nanocomposite which proves the high catalytic performance of the nanocomposites. The first-principles calculation was employed to elaborate the synergistic effect, and the findings demonstrate that the presence of graphene in the catalyst can enhance the catalytic effect via reducing the activation energy barrier by ∼17% in the reaction of AP thermal decomposition.

Zinc sulfide (ZnS) exhibits promise in sodium-ion batteries (SIBs) because of its low operation voltage and high theoretical specific capacity. However, pristine ZnS is not adequate in realizing rapid and robust sodium storage owing to its low reversibility, poor structure stability, and sluggish kinetics. To date, most efforts focus on utilizing carbonaceous incorporation to improve its electrochemical performances. Nevertheless, it remains an arduous challenge for realizing superior rate capability while obtaining stable cycling. Herein, inspired by the crystal structure of hexagonal ZnIn2S4, which possesses an intrinsic layered feature with larger unit-cell volume versus that of ZnS, indium incorporation is thus deployed as an immediate remedy. In/ex situ investigations combined with density functional theory calculations are conducted to reveal the superior kinetics, high reversibility, and good structure stability of ZnIn2S4. Notably, the formed indium-based derivatives during cycling manifest a Na+ (de)intercalation process, thereby exciting a synergetic mechanism to stabilize electrochemical cycling. As a result, the electrochemical performances of Zn-based sulfide are significantly improved via the indium incorporation. Furthermore, a full cell based on the ZnIn2S4 anode with the superior electrochemical performance is developed. This work provides an effective tactic of heteroatom incorporation for optimizing structure as well as exciting a complementary reaction process toward developing superior anodes for high-performance alkali-ion batteries.

Tin-based materials with high specific capacity have been studied as high-performance anodes for energy storage devices. Herein, a SnOx (x = 0, 1, 2) quantum dots@carbon hybrid is designed and prepared by a binary oxide-induced surface-targeted coating of ZIF-8 followed by pyrolysis approach, in which SnOx quantum dots (under 5 nm) are dispersed uniformly throughout the nitrogen-containing carbon nanocage. Each nanocage is cross-linked to form a highly conductive framework. The resulting SnOx@C hybrid exhibits a large BET surface area of 598 m2 g-1, high electrical conductivity, and excellent ion diffusion rate. When applied to LIBs, the SnOx@C reveals an ultrahigh reversible capacity of 1824 mAh g-1 at a current density of 0.2 A g-1, and superior capacities of 1408 and 850 mAh g-1 even at high rates of 2 and 5 A g-1, respectively. The full cell assembled using LiFePO4 as cathode exhibits the high energy density and power density of 335 Wh kg-1 and 575 W kg-1 at 1 C based on the total active mass of cathode and anode. Combined with in situ XRD analysis, the superior electrochemical performance can be attributed to the SnOx-ZnO-C asynchronous and united lithium storage mechanism, which is formed by the well-designed multifeatured construction composed of SnOx quantum dots, interconnected carbon network, and uniformly dispersed ZnO nanoparticles. Importantly, this designed synthesis can be extended for the fabrication of other electrode materials by simply changing the binary oxide precursor to obtain the desired active component or modulating the type of MOFs coating to achieve high-performance LIBs.

Carbon-based metal-free catalysts exhibit great applications in electrochemical CO2 reduction (ECR), while most studies merely focus on large-sized carbons with limited ratio of surface atoms for engineering to create surface active centers. Here, we report a joint treatment of C60 by heating and plasma to induce a dramatic performance promotion during ECR. The electrochemical measurements indicate the Faraday efficiency for ECR toward CO production kept at high level over 80% in a wide potential region from − 0.4 to − 0.7 V versus RHE, with the highest value reaching 96.8%. The physical characterization reveals that fragmentation of C60 occurs together with N/O doping, both of which could induce change in electron structure, causing the formation of *COOH intermediate and ultimately leading to the optimized activity and selectivity for CO production. This treatment route was further revealed to be applicative for other carbon materials, e.g., single-walled carbon nanotube, to promote its ECR activity and selectivity.

Suppression of type I interferon (IFN) response is one pathological outcome of the infection of highly pathogenic human coronaviruses. To effect this, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 encode multiple IFN antagonists. In this study, we reported on the IFN antagonism of SARS-CoV-2 main protease NSP5. NSP5 proteins of both SARS-CoV and SARS-CoV-2 counteracted Sendai virus-induced IFN production. NSP5 variants G15S and K90R commonly seen in circulating strains of SARS-CoV-2 retained the IFN-antagonizing property. The suppressive effect of NSP5 on IFN-β gene transcription induced by RIG-I, MAVS, TBK1 and IKKϵ suggested that NSP5 likely acts at a step downstream of IRF3 phosphorylation in the cytoplasm. NSP5 did not influence steady-state expression or phosphorylation of IRF3, suggesting that IRF3, regardless of its phosphorylation state, might not be the substrate of NSP5 protease. However, nuclear translocation of phosphorylated IRF3 was severely compromised in NSP5-expressing cells. Taken together, our work revealed a new mechanism by which NSP5 proteins encoded by SARS-CoV and SARS-CoV-2 antagonize IFN production by retaining phosphorylated IRF3 in the cytoplasm. Our findings have implications in rational design and development of antiviral agents against SARS-CoV-2.

N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is installed by a multi-component writer complex; however, the exact roles of each component remain poorly understood. Here we show that a potential E3 ubiquitin ligase Hakai colocalizes and interacts with other m6A writer components, and Hakai mutants exhibit typical m6A pathway defects in Drosophila, such as lowered m6A levels in mRNA, aberrant Sxl alternative splicing, wing and behavior defects. Hakai, Vir, Fl(2)d and Flacc form a stable complex, and disruption of either Hakai, Vir or Fl(2)d led to the degradation of the other three components. Furthermore, MeRIP-seq indicates that the effective m6A modification is mostly distributed in 5’ UTRs in Drosophila, in contrast to the mammalian system. Interestingly, we demonstrate that m6A modification is deposited onto the Sxl mRNA in a sex-specific fashion, which depends on the m6A writer. Together, our work not only advances the understanding of mechanism and regulation of the m6A writer complex, but also provides insights into how Sxl cooperate with the m6A pathway to control its own splicing.

Assembly of the top-down graphene units mostly results in 3D porous structure with randomly organized pores. The direct bottom-up synthesis of macroscopic 2D graphene sheets with organized pores are long sought in materials chemistry field, but rarely achieved. Herein, we present a self-catalysis-assisted bottom-up route using L-glutamic acid and iron chloride as starting materials for the fabrication of the millimeter-sized few-layer graphene sheets with aligned porous channels parallel to the 2D direction. The amino- and carboxyl-functional groups in L-glutamic acid can coordinate with iron cations, thus allowing an atomic dispersion of iron cations. The pyrolysis thus initiated the growth of graphene catalyzed by in-situ generated iron nanoparticles, and a dynamic flow of iron nanoparticles eventually led to the formation of millimeter-sized few-layer graphene sheets with aligned channels (60–85 nm in diameter). Used as anodes in lithium-ion batteries, these graphene sheets showed a good rate capability (142 mA h g−1 at 2 A g−1) and high capacity retention of 93% at 2 A g−1 after 1200 cycles. Kinetic analysis revealed that lithium ions storage was dominated by diffusion behavior and capacitive behavior together, in that graphene sheets with aligned channels could accelerate electron transfer and shorten lithium ions transport pathway. This work provides a novel approach to prepare unique porous graphene materials with specific structure for energy storage.

Glass-based materials are usually considered as excellent seals for jointing adjacent components in planar solid oxide fuel cells, but the uncontrollable crystallization in the glass may cause delamination and micro-cracks in such seals. To solve this problem, Al2O3 ceramic particles were added to a BaO–CaO–Al2O3–B2O3–SiO2 glass system to reduce negative effects caused by crystalline phase on the gas tightness and the joint strength in the seals. At an operating temperature of 750 °C, the glass-based seals with 20 wt% Al2O3 addition (GA80) exhibited extremely low leakage rates (~0.002 sccm/cm under an input gas pressure of 13.6 kPa) and higher shear strength (3.31 MPa). The Al2O3 ceramic addition and the crystalline phase BaAl2Si2O8 reinforced the glass matrix. Further thermal cycle analyses indicated that leakage rates for the GA80 seals remained at around 0.0025 sccm/cm after 10 thermal cycles, which was consistent with minor microstructural change and good interface bonding. Single cell testing with of GA80 seals was performed and the results demonstrated stable electrochemical performance through 6 thermal cycles at an open circuit voltage of 1.16–1.18 V, as well as a power density above 546 mW/cm2 at a current density of 925 mA/cm2. These results showed the high thermal cycle stability of the glass/Al2O3 composite seals in intermediate temperature planar solid oxide fuel cells.

Baicalein, the primary flavonoid derived from the roots of Scutellaria baicalensis Georgi, is known to exhibit anticancer effects against different types of cancer. However, the anticancer activity and underlying mechanisms of baicalein on cholangiocarcinoma (CCA) have not been elucidated. Here, our results showed that baicalein inhibited the viability and proliferation of CCA cells in a dose and time-dependent manner. Besides, baicalein also induced cell apoptosis and cell cycle arrest by regulating cell cycle associated proteins and Bcl-2 family proteins expression. More importantly, baicalein also suppressed the migration and invasion by reducing the expression of MMP-2 and MMP-9 proteins, as well as decreased the aerobic glycolysis of CCA cells by reducing Hexokinase and Glucose-6-phosphate. In the mechanistic study, the phosphorylation of IκBα, AKT and STAT3 were all significantly decreased by baicalein in vitro and in vivo. Furthermore, baicalein also inhibited the tumor growth in subcutaneous xenograft model of mice. These findings indicate that baicalein has potent anticancer activities by suppressing multiple malignant phenotypes and most probably through inhibiting the activation of the AKT/NF-κB and STAT3 signaling pathway. Thus, it has the potential to be developed as an anticancer agent to enhance clinical standards of care for patients with CCA.

We intended to characterize functional relevance of microRNA (miR)-224-3p in endothelial cell (EC) apoptosis and reactive oxygen species (ROS) accumulation in atherosclerosis, considering also the integral involvement of histone deacetylase 1 (HDAC1)-mediated hypoxia-inducible factor-1α (HIF1α) deacetylation. The binding affinity between miR-224-3p and Fos-like antigen 2 (FOSL2) was predicted and validated. Furthermore, we manipulated miR-224-3p, FOSL2, HDAC1, and HIF1α expression in oxidized low-density lipoprotein (ox-LDL)-induced ECs, aiming to clarify their effects on cell activities, inflammation, and ROS level. Additionally, we examined the impact of miR-224-3p on aortic atherosclerotic plaque and lesions in a high-fat-diet-induced atherosclerosis model in ApoE−/− mice. Clinical atherosclerotic samples and ox-LDL-induced human aortic ECs (HAECs) exhibited low HDAC1/miR-224-3p expression and high HIF1α/FOSL2 expression. miR-224-3p repressed EC cell apoptosis, inflammatory responses, and intracellular ROS levels through targeting FOSL2. HIF1α reduced miR-224-3p expression to accelerate EC apoptosis and ROS accumulation. Moreover, HDAC1 inhibited HIF1α expression by deacetylation, which in turn enhanced miR-224-3p expression to attenuate EC apoptosis and ROS accumulation. miR-224-3p overexpression reduced atherosclerotic lesions in vivo. In summary, HDAC1 overexpression may enhance the anti-atherosclerotic and endothelial-protective effects of miR-224-3p-mediated inhibition of FOSL2 by deacetylating HIF1α, underscoring a novel therapeutic insight against experimental atherosclerosis., Graphical Abstract, The study mainly addressed the suppressive role of HDAC1-mediated deacetylation of HIF1α in atherosclerosis progression, which was associated with miR-224-3p-mediated inhibition of FOSL2, thus highlighting a potential therapeutic action against atherosclerosis.

La0.5(Ba0.75Ca0.25)0.5Co0.8Fe0.2O3-δ, a simple perovskite cathode material with high electrical conductivity (940 S cm−1 at 600 °C) and impressive surface catalytic activity, was prepared and used in proton-conducting solid oxide fuel cells. As its thermal expansion coefficient is higher than that of the electrolyte material BaZr0.1Ce0.7Y0.1Yb0.1O3-δ, they were combined and used as a composite cathode. The crystal structure, chemical compatibility, electrical conductivity, cell performance, and the oxygen reduction reaction of the cathode material were explored, and we found that the single fuel cell developed with the composite cathode achieved excellent electrochemical performance, with both a low polarization resistance and high peak power density (0.044 Ω cm2 and 1102 mW cm−2 at 750 °C, respectively). Outstanding stability was also achieved, as indicated by a long-term 100-h test. Additionally, the rate-limiting steps of the oxygen reduction reaction were the oxygen adsorption, dissociation, and diffusion processes.

This article presents a GaN driver operating at a switching frequency variable from 10 to 30 MHz to achieve reliable and efficient power conversion for automotive electronics applications. An active bootstrap (BST) balancing (ABB) technique is presented to stabilize the BST rail voltage by sensing $V_{\mathrm{ SW}}$ and controlling BST rail charging. Meanwhile, a $V_{\mathrm{ SW}}$ dual-edge dead-time ( $t_{\mathrm{ dead}}$ ) modulation senses instant $V_{\mathrm{ IN}}$ and $I_{O}$ and generates optimal $t_{\mathrm{ dead}}$ for $V_{\mathrm{ SW}}$ trailing and leading edges, achieving zero-voltage switching (ZVS) turn-on for GaN power switches. To operate at high frequency and retain high efficiency, pulse-based dynamic up- and down-level shifters are developed to achieve sub-nanosecond propagation delay with a quiescent current of 0.5 $\mu \text{A}$ . To validate this work, a switching power converter prototype is implemented using a 0.35- $\mu \text{m}$ high-voltage (HV) BCD process. It maintains a constant 5.1-V BST rail voltage to prevent GaN FET from destructive breakdown and accomplishes 0.9-to-3.7-ns $t_{\mathrm{ dead}}$ and 3.7-to-10.4-ns $t_{\mathrm{ dead}}$ for $V_{\mathrm{ SW}}$ trailing and leading edge, respectively, in response to load current $I_{O}$ change from 0.01 to 1.2 A. The proposed techniques jointly improve the efficiency by 8.3%, which peaks at 90.7% for 12-to-5-V conversion and 88% for 40-to-5-V conversion.

Traditional ozone sensing and removal materials still suffer from high energy consumption and low efficiency. Thus, seeking new ozone-responsive materials with high efficiency and broad working conditions is of great significance. Herein, we first developed covalent organic frameworks (COFs) for smart sensing and efficient removal of ozone. Notably, imine-based COFs possess dramatically fast optical responses (

Metal halide perovskites and colloidal quantum dots (QDs) are two emerging classes of photoactive materials that have attracted considerable attention for next-generation high-performance solution-processed solar cells. In particular, the hybridization of these two types of materials has recently demonstrated remarkable performance enhancement due to the complementary nature of the two constituents. In this review, we will highlight the recent progress of QDs and perovskite hybridization in solar cell applications. More specifically, the unique properties of monophase perovskite QDs will be summarised, and are demonstrated by homogeneously hybridizing perovskite QDs into the perovskite lattice. We also discuss the recent progress in heterogeneously hybridizing discrete colloidal QDs into perovskite layers which results in significant enhancement in perovskite film stability as well as corresponding solar cell performance improvement. PbS QDs, other chalcogenide QDs, and emerging two-dimensional QDs are further accounted through multiple methods, such as constructing bilayer architectures and core–shell structures or blending multiple QDs into perovskite layers. In the end, an outlook perspective of this field has been proposed to point out several challenges and possible solutions.

With the increased development of wearable electronics, flexible zinc ion batteries (ZIBs) have attracted widespread attention owing to their low cost, superior safety, and simple fabrication process. Nevertheless, the limited active mass loading and low specific capacity remain challenges to be overcome. Herein, an effective in situ growth strategy is used to boost the mass loading and specific capacity of flexible ZIBs. We employed a mussel-derived polydopamine layer as an inductive catalyst to prompt the growth of flower-like δ-MnO2 on carbon cloth, which demonstrated strong adhesion to the surface, high mass loading, and excellent flexibility. In addition, the formed 3D conductive and supporting networks contribute to the realization of superior long cycle life, as well as a high specific capacity. As a result, the as-obtained flexible cathode can achieve a high initial discharge capacity of 1.3 mA h cm−2 at a current density of 1 mA cm−2 and a reversible capacity of 0.25 mA h cm−2 at 10 mA cm−2 for 10 000 cycles. Moreover, its reaction mechanism in ZIBs was analyzed via a series of ex situ characterization techniques, and the results suggest that the charge–discharge behavior is determined based on the Zn2+ (de-)intercalation in the δ-MnO2 interlayer. Remarkably, the as-developed flexible cathode is assembled into a flexible quasi-solid-state device, which shows excellent flexibility and can easily power one LED-based device, which has significant application prospects in wearable electronics. This work provides a novel tactic for the design of flexible batteries with high active mass loading and excellent electrochemical performance via employing polydopamine as an inductive catalyst.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by the novel lineage B betacoroanvirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant mortality, morbidity, and socioeconomic disruptions worldwide. Effective antivirals are urgently needed for COVID-19. The main protease (Mpro) of SARS-CoV-2 is an attractive antiviral target because of its essential role in the cleavage of the viral polypeptide. In this study, we performed an in silico structure-based screening of a large chemical library to identify potential SARS-CoV-2 Mpro inhibitors. Among 8,820 compounds in the library, our screening identified trichostatin A, a histone deacetylase inhibitor and an antifungal compound, as an inhibitor of SARS-CoV-2 Mpro activity and replication. The half maximal effective concentration of trichostatin A against SARS-CoV-2 replication was 1.5 to 2.7µM, which was markedly below its 50% effective cytotoxic concentration (75.7µM) and peak serum concentration (132µM). Further drug compound optimization to develop more stable analogues with longer half-lives should be performed. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of SARS-CoV-2.

Background: The aim of this study was to understand physical characteristics of Embosphere microspheres for the clinical use of microsphere chemotherapy embolization of liver cancer. Methods: The morphology of Embosphere microspheres in different states, including static, oscillating, and in a magnetic field was observed with the naked eye. Ninety-five patients diagnosed with primary hepatocellular carcinoma (HCC) were separated into 3 groups based on the types of embolic material as follows: 32 cases of sole microspheres, 34 cases of iodinated oil (17 cases with additional application of gelatin sponge particle), and 29 cases of iodinated oil + Embosphere microspheres. Results: The diameter of the microspheres ranged from 100 to 300 μm, with a sedimentation rate υ = 0.0375 cm/s in physiological saline. The diameter of microspheres ranged from 300 to 500 μm, with a sedimentation rate υ = 0.1875 cm/s. The swelling rate of microspheres was 90%. Microspheres showed nondirectional movement in a 1.5- or 3.0-T magnetic field during magnetic resonance imaging. A volumetric ratio of 1:1.4–1:1.5 between microspheres and contrast agent resulted in optimal suspension properties. Microspheres appeared circular with a smooth surface upon water adsorption. Microsphere embolism was observable in blood vessels of pathological sections. The surface of microspheres can adsorb 5-fluorouracil and arsenic trioxide. There are statistically significant differences in local-regional tumor control conditions among patients treated with sole microspheres, iodinated oil, and iodinated oil + microspheres during transarterial chemoembolization. Conclusions: Embosphere microspheres can be used to embolize patients with rupture and hemorrhage of HCC. Embosphere microsphere embolization is superior to iodinated oil and iodinated oil + microsphere for HCC.

Owing to the favorable energy efficiency and environmental compatibility, capacitive deionization (CDI) has been greatly developed as a potential technology to overcome the ever-growing global water shortage. Herein, an effective and simple strategy is reported to boost the desalination performance by 30 percent through an expansion of interlayer spacing. The final redox active hybrid CDI material consists of WS2 nanoflowers embedded in a highly conductive free-standing rGO-CNT (WS2/rGO-CNT) aerogel as an anode and rGO-CNT aerogel as a cathode. WS2 is applied as a redox-active material for sodium ion intercalation, and three-dimensional (3D) rGO-CNT facilitates the diffusion of the ions to boost the reaction kinetics. Upon charging/discharging, sodium ions intercalate/deintercalate into/from the WS2 lattice structure which is confirmed via in situ XRD measurements, and chloride ions are physically adsorbed/desorbed by the rGO-CNT aerogel. Benefiting from the synergistic effect between the highly conductive and porous rGO-CNT framework and WS2 nanoflowers with a tuned structure, the as-assembled HCDI device enables stable desalination performance with a superior removal capacity of 80 mg g−1, and an excellent removal rate of 3.9 mg g−1 min−1.

Upgrading liquid electrolytes with all-solid-state electrolytes (ASEs) or quasi-solid-state electrolytes (QSEs) for solid-state batteries (SBs) have emerged not only to address the intrinsic disadvantages of traditional liquid lithium ion batteries, but also to offer more possibilities for the development of new battery chemistries. In this work, a novel rambutan-like yolk–shell-structured porous γ-AlOOH microsphere with a large specific surface area of 262.92 m2 g−1 was firstly obtained by a simple hydrothermal synthesis route, which was then utilized as a robust framework to assemble QSE via encapsulating abundant liquid electrolyte (LE). The obtained γ-AlOOH-QSE exhibits a high ionic conductivity of 4.0 × 10−3 S cm−1, a large lithium ion transference number (tLi+) of 0.76, as well as a wide electrochemical window of 4.72 V vs. Li/Li+. Moreover, the assembled cell of LiFePO4/γ-AlOOH-QSE/Li could maintain a high specific capacity of 144.4 mA h g−1 even after 120 cycles with almost negligible capacity decay, which could be mainly attributed to the excellent interfacial compatibility, prominent performance in suppressing lithium dendrite growth upon cycling (rigid characteristic), as well as the high ionic conductivity of γ-AlOOH-QSE (intrinsic advantage). This work could not only expand the applications of QSE with cost-effective aluminum-based oxides with facile fabrication strategy, but also will shed light on the construction of SEs with more integrated QSEs and ASEs in the field of advanced energy storage.

Colorless polyimide (PI) films with outstanding mechanical and thermal properties are highly demanded in flexible electronics. Herein three 4,4′-diaminodiphenyl ether (ODA)-based diamines with different substituents (–CH3, –CF3) and substitution positions (ortho and meta positions) were synthesized. After reacting with a combination of 1,2,4,5-cyclohexanetetracarboxylic dianhydride (CHDA) and 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) in a typical sequential reaction manner, four highly transparent copolyimide films with excellent mechanical strength, high heat-resistance and superior fracture toughness were fabricated. A copolyimide film made using m-3F-ODA exhibits a fairly high transmittance at 400 nm of up to 86.8%, tensile strength as high as 102 MPa, tensile modulus of 2.76 GPa and glass transition temperature above 308 °C. The desirable solubility enables the prepared PIs to be readily cast from solution into robust films. All these encouraging results make these PI films potential substrates in place of ultrathin glass in flexible displays.

Capture and controlled release of singlet oxygen (1O2) are of great significance but very challenging due to its very short lifetime and high reactivity. Addressing this challenge, we rationally designed and fabricated a highly crystalline, robust, and porous three-dimensional covalent organic framework (3D COF) by installing functional anthracene moieties on its skeleton for 1O2 related applications. Attributed to its open networks, regular channels, and light skeletal density, the active anthracene sites in the 3D COF can be fast and fully accessed, hence affording superior performance compared with other contrastive materials such as 2-dimensional COFs and amorphous polymers. Notably, the 3D COF displays the current record-high 1O2 capture rate among all reported porous materials, verified by various characterization techniques and rational analysis. Furthermore, we used the 3D COF platform as a stimuli-responsive smart material for anti-fake applications. This study not only provides an outstanding platform for 1O2 capture and release but also extends the application scopes of COFs.

Rationale: Little is known about the roles of proteoglycans in esophageal cancer. This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC). Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells. Chemokine array was used to identify differentially secreted factors from SRGN-overexpressing cells. Binding between SRGN and potential interacting partners was evaluated using proximity ligation assay and co-immunoprecipitation. The glycosaminoglycan (GAG) chains of SRGN were characterized using fluorophore-assisted carbohydrate electrophoresis. Tissue microarray and serum samples were used to determine the correlation of SRGN expression with clinicopathological parameters and patient survival. Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. SRGN-knockdown suppressed tumorigenic hallmarks. These SRGN-elicited functions were carried out in an autocrine manner by inducing the secretion of midkine (MDK), which was further identified as a novel binding partner of SRGN for the formation of a SRGN/MDK/CD44 complex. In addition, SRGN interacted with MDK and matrix metalloproteinase 2 in ESCC via its GAG chains, which were mainly decorated with chondroitin sulfate comprising of ∆di-4S and ∆di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. Conclusions: This study provides the first evidence that elevated serum SRGN has prognostic significance in patients with ESCC, and sheds light on the molecular mechanism by which elevated circulating SRGN in cancer patients might promote cancer progression.

BACKGROUND Gut tryptophan (Trp) metabolites are produced by microbiota and/or host metabolism. Some of them have been proven to promote or inhibit colorectal cancer (CRC) in vitro and animal models. We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC. AIM To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota. METHODS Seventy-nine patients with colorectal neoplastic lesions (33 with colon adenoma and 46 with sporadic CRC) and 38 healthy controls (HCs) meeting the inclusion and exclusion criteria were included in the study. Their demographic and clinical features were collected. Fecal Trp, kynurenine (KYN), and indoles (metabolites of Trp metabolized by gut microbiota) were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut barrier marker and indoleamine 2,3-dioxygenase 1 (IDO1) mRNA were analyzed by quantitative real-time polymerase chain reaction. Zonula occludens-1 (ZO-1) protein expression was analyzed by immunohistochemistry. The gut microbiota was detected by 16S ribosomal RNA gene sequencing. Correlations between fecal metabolites and other parameters were examined in all patients. RESULTS The absolute concentration of KYN [1.51 (0.70, 3.46) nmol/g vs 0.81 (0.64, 1.57) nmol/g, P = 0.036] and the ratio of KYN to Trp [7.39 (4.12, 11.72) × 10-3 vs 5.23 (1.86, 7.99) × 10-3, P = 0.032] were increased in the feces of patients with CRC compared to HCs, while the indoles to Trp ratio was decreased [1.34 (0.70, 2.63) vs 2.46 (1.25, 4.10), P = 0.029]. The relative ZO-1 mRNA levels in patients with CRC (0.27 ± 0.24) were significantly lower than those in HCs (1.00 ± 0.31) (P < 0.001), and the relative IDO1 mRNA levels in patients with CRC [1.65 (0.47-2.46)] were increased (P = 0.035). IDO1 mRNA levels were positively associated with the KYN/Trp ratio (r = 0.327, P = 0.003). ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio (P = 0.035 and P = 0.009, respectively). In addition, the genera Asaccharobacter (Actinobacteria) and Parabacteroides (Bacteroidetes), and members of the phylum Firmicutes (Clostridium XlVb, Fusicatenibacter, Anaerofilum, and Anaerostipes) decreased in CRC and exhibited a positive correlation with indoles in all subjects. CONCLUSION Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism, and may be involved in the pathogenesis of CRC.

The low charge storage in intercalation-type reaction and the large volume change induced by conversion/alloying reactions greatly limit the practical selection of anodes in sodium-ion batteries (S...

WRKY group transcription factors of model plants and major crops are confirmed to play essential roles in stress responses, senescence, secondary metabolism processes and hormone signal transduction. Previous studies have identified 81 HbWRKY genes from Hevea brasiliensis (the Para rubber tree), but the functions of HbWRKYs in response to abiotic stresses and leaf senescence are unclear. In this study, one novel group IIc WRKY transcription factor named HbWRKY82 was identified and characterized as a stress-associated WRKY in rubber tree. Transient expression and transcriptional activation analyses indicated that HbWRKY82 encoded a nuclear protein and functioned as a transcription activator. The transcription levels of HbWRKY82 were induced by by exogenous Ethrel (ethylene releaser) and abscisic acid (ABA) stimulations, down-regulated in tapping panel dryness rubber trees, and also exhibits significant decrease during the progression of leaf senescence. Overexpression of HbWRKY82 in Arabidopsis improved the tolerance to dehydration and salinity, and decreased the sensitivity to exogenous ABA. Moreover, real-time quantitative PCR analysis demonstrated that HbWRKY82 regulated the transcriptional expression of several stress-responsive genes (DREB1A, ERD10, HKT1, P5CS, RD22, RD29B, SKOR), leaf senescence marker genes (EIN3, WRKY53, NAP), ROS-related genes (RbohD, CSD1, CSD2, FSD3) and hormone signaling genes (EIN3, ABF3, ABF4). Collectively, our findings suggested that HbWRKY82 might function as an important transcriptional regulator in Ethrel -and ABA-mediated leaf senescence and abiotic stress responses, and also be involved in tapping panel dryness, latex flow and regeneration processes of rubber trees via participating in the ET and ROS signaling pathways. This article is protected by copyright. All rights reserved.