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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

There is a clear, unmet clinical need to identify new drugs to treat individuals with asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) in whom current medications are either inactive or suboptimal. In preclinical models, EP4-receptor agonists display efficacy, but their mechanism of action is unclear. In this study, using human bronchial epithelial cells as a therapeutically relevant drug target, we hypothesized that changes in gene expression may play an important role. Several prostanoid receptor mRNAs were detected in BEAS-2B cells, human primary bronchial epithelial cells (HBECs) grown in submersion culture and HBECs grown at an air-liquid interface with PTGER4 predominating. By using the activation of a cAMP response element reporter in BEAS-2B cells as a surrogate of gene expression, Schild analysis determined that PTGER4 mRNAs encoded functional EP4-receptors. Moreover, inhibitors of phosphodiesterase 4 (roflumilast N-oxide [RNO]) and cAMP-dependent protein kinase augmented and attenuated, respectively, reporter activation induced by 2-[3-[(1R,2S,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-[2-(methoxymethyl)phenyl]pent-1-enyl]-5-oxo-cyclopentyl]sulphanylpropylsulphanyl] acetic acid (ONO-AE1-329), a selective EP4-receptor agonist. ONO-AE1-329 also enhanced dexamethasone-induced activation of a glucocorticoid response element reporter in BEAS-2B cells, which was similarly potentiated by RNO. In each airway epithelial cell variant, numerous genes that may impart therapeutic benefit in asthma, COPD, and/or IPF were differentially expressed by ONO-AE1-329, and those changes were often augmented by RNO and/or dexamethasone. We submit that an EP4-receptor agonist, either alone or as a combination therapy, may be beneficial in individuals with chronic lung diseases in whom current treatment options are inadequate. SIGNIFICANCE STATEMENT Using human bronchial epithelial cells as a therapeutically relevant drug target, we report that EP4-receptor activation promoted gene expression changes that could provide therapeutic benefit in individuals with asthma, COPD, and IPF in whom current treatment options are ineffective or suboptimal.

Zn-doped PrBa0.9Ca0.1Co2-xZnxO5+δ (PBCCZx) with x equaling 0, 0.05, 0.10, 0.15, and 0.2, designated as PBCCZ00, PBCCZ05, PBCCZ10, PBCCZ15, and PBCCZ20, respectively, are prepared and investigated in the aspects of crystal structure, thermal expansion behavior, defect chemistry, and electrochemical performance as the cathode of proton-conducting solid oxide fuel cells (H–SOFCs). With the increase of the content of doped Zn, the thermal expansion coefficient of PBCCZx remains unchanged essentially. But the bulk and surface concentrations of oxygen vacancy are increased, and the maximum power density (MPD) of the cells at 750 °C with PBCCZx-BaZr0.1Ce0.7Y0.1Yb0.1O3-δ (BZCYYb) composite cathodes are improved from 335 (x = 0) to 876 (x = 0.15) mW cm−2. With the PBCCZ15-BZCYYb cathode, the MPD of the cell increases with temperature from 299 mW cm−2 at 600 °C to 876 mW cm−2 at 750 °C with a reduction of cell polarization resistance from 0.68 to 0.04 Ω cm2 accordingly.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH3-THF), which is required for the de novo biosynthesis of methionine in bacteria. In this study, we identified Rv2172c as an MTHFR in M. tuberculosis through in vitro and in vivo analyses and determined that the protein was essential for the in vitro growth of the bacterium. Subsequently, we constructed rv2172c R159N and L214A mutants in M. tuberculosis, and found that these mutants were more sensitive to the antifolates para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Combining biochemical and genetic methods, we found that rv2172c R159N or L214A mutation impaired methionine production, leading to increased susceptibility of M. tuberculosis to PAS, which was largely restored by adding exogenous methionine. Moreover, overexpression of rv2172c in M. tuberculosis could increase methionine production and lead to PAS resistance. This research was the first to identify an MTHFR in M. tuberculosis and revealed that the activity of this enzyme was associated with susceptibility to antifolates. These findings have particular value for anti-tubercular drugs design for the treatment of drug-resistant TB.

A–Ar–A-type small molecule (SM) of Py-2DTOBT and Py-2DTOBTPh with an Ar(A–D)2 framework were synthesized, in which 2,7-pyrene (Py) and alkoxyl-substituted benzothiadiazole (OBT) were, respectively, used as the central aryl (Ar) and arm acceptor (A), while 3-phenanthrene (Ph) was used as a terminal donor (D) in Py-2DTOBTPh. By comparison with the parent SM of Py-2DTBT, where 2,7-pyrene (Py) and benzothiadiazole (BT) were used as the central aryl (Ar) and arm acceptor (A), the effects of non-covalent interactions and the terminal group on optical, electrochemical, and photovoltaic properties were investigated. The gradually improved photovoltaic performances were observed among Py-2DTBT, Py-2DTOBT, and Py-2DTOBTPh based organic solar cells. A power conversion efficiency (PCE) of 2.83% was obtained in the Py-2DTOBTPh/PC71BM-based device, which is a 53% improvement related to that of Py-2DTOBT and three times enhanced related to that of Py-2DTBT(Py-2DTOBT:PCE of 1.86%, Py-2DTBT:PCE of 0.74%).

A 5-cell stack with external manifold is thermal cycled between room temperature and 750 °C fifteen times. The electric performances after each cycle are measured and compared. The stack has an initial peak output of 328.44 W and shows excellent stability in thermal cycling. The average operating voltage degradation rate is only 0.8% corresponding each thermal cycle. A cell from the stack is randomly chosen for electrochemical evaluation. Its performance is found to be comparable to a cell which is not thermal cycled. Post-test examination shows deterioration of cathode contact materials at points of contact and cracks throughout the oxide layer between corrugated and bipolar plates to be the main causes of the degradation.

Considering the fact that its existence is abundant while maintaining the ability to generate freshwater while burning, methane hydrates have been classified as sources of sustainable energy. China currently maintains an international role in developing technology meant to explore offshore methane hydrates buried under the mud of the seabed, their primary laboratory being the South China Sea. However, such a process does not come without its hazards and fatal consequences, ranging from the destruction of the flora and fauna, the general environment, and—the greatest hazard of all—the cost of human life. The United Nations Convention on the Law of the Sea (hereinafter ‘UNCLOS’), being an important international legal regime and instrument, has assigned damage control during the exploration of methane hydrates, as being the responsibilities and liability of individual sovereign states and corporations. China adopted the Deep Seabed Mining Law (hereinafter the DSM Law) on 26 February 2016, which came into force on the 1 of May 2016; a regulation providing the legal framework also for the Chinese government’s role in methane hydrate exploratory activities. This article examines the role of the DSM Law and its provisions, as well as several international documents intended to prevent transboundary environmental harm from arising, as a result of offshore methane hydrate extraction. Despite the obvious risk of harm to the environment, the DSM Law has made great strides in regulating exploratory activities so as to meet the criteria of the UNCLOS. However, this article argues that neither the UNCLOS nor the DSM Law are adequately prepared to address transboundary harm triggered by the exploitation of offshore methane hydrates. In particular, the technology of such extraction is still at an experimental stage, and potential risks remain uncertain—and even untraceable—for cross-jurisdictional claims. The article intends to seek available legal instruments or models, to overhaul the incapacity within the current governing framework, and offers suggestions supporting national and international legislative efforts towards protecting the environment during methane hydrate extraction.

In modern power delivery systems, there has been an up-rising trend of migrating conventional two-stage dc–dc power conversion architecture to a single-stage one, in order to accomplish better efficiency and power density. In response to such a trend, this article presents a gallium nitride (GaN)-based power converter design that achieves direct 48-/1-V dc–dc power conversion with a single-stage double step-down (DSD) architecture. Operating at 2 MHz, it pushes the equivalent minimum duty ratio to a record low level of 2.1%. In order to improve closed-loop regulation, an adaptive ON- and OFF-time (AO2T) control with elastic ON-time modulation is proposed for both steady-state and transient response enhancement. For reinforced reliability in the dual-phase operation, a master-phase mirroring technique enables adaptive master–slave phase operation, accomplishing automatic phase current balancing. An IC prototype is implemented on a 180-nm high voltage (HV) bipolar, CMOS DMOS (BCD) process, with an active die area of 1.46 mm2. It achieves peak efficiencies of 85.4%, 79%, and 56.8% at 100 kHz, 250 kHz, and 2 MHz, respectively.

In this study, the multifunctional carbon nitride based composite graphitic-C3N4 (g-C3N4)/TiO2/Ag was prepared through a simple and efficient vacuum freeze-drying route. TiO2 and Ag nanoparticles were demonstrated to decorate onto the surface of g-C3N4 sheet. In the ultraviolet–visible absorption test, a narrower band gap and red-shift of light absorption edge were observed for g-C3N4/TiO2/Ag compared to pristine g-C3N4 and single-component modified g-C3N4/TiO2. The photodegradation property of g-C3N4/TiO2/Ag was investigated toward the degradation of methylene blue (abbreviated as MB) under the irradiation of visible light. These results indicated that the degradation performance of organic dyes for g-C3N4/TiO2/Ag was obviously improved compared with g-C3N4/TiO2 and g-C3N4. The reaction rate constant of MB degradation for g-C3N4/TiO2/Ag was 4.24 times higher than that of pristine g-C3N4. In addition, such rationally constructed nanocomposite presented evidently enhanced antibacterial performance against the Gram-negative Escherichia coli. Concentration dependent antibacterial performance was systematically investigated. And 84% bacterial cell viability loss had been observed at 500 μg/mL g-C3N4/TiO2/Ag within 2 h visible light irradiation.

In this study, the effect of particulate matter type, temperature, oil type and weathering degree on the interaction between dispersed crude oil droplets and particulate matter was investigated. The increase of total petroleum hydrocarbon (TPH) percentage in oil-particle aggregates (OPAs) could be attributed to the increase of oil polarity or viscosity. For small size particulate matter, there was a fine dependence relationship between the TPH percentage in OPAs and the oil viscosity and the content of polar components, respectively (R2 > 0.7502). And the total organic carbon content also played an important role in the formation of OPAs. The petroleum hydrocarbon extracts of OPAs showed a decrease in short-carbon-chain components and a relative increase in long-carbon-chain compounds. Petroleum hydrocarbon compounds trapped by three types of particulate matter exhibited a similar change tendency, but there was no apparent difference in the residual TPH percentage in water.

The purpose of this study was to efficiently convert the sugary food waste (SFW) to 5-hydroxymethylfurfural (5-HMF) by ultrasound-[Bmim]Cl pretreatment in ionic liquids (ILs)-ion exchange resin system. The effect of ultrasonic pretreatment on SFW and the effect of ultrasonic frequency, ILs, acid resin and catalyst load on SFW conversion were studied. The kinetic curve and the relationship between products and intermediates were studied. In addition, the structure of SFW was also studied by FT-IR and SEM. The results indicated ultrasound-[Bmim]Cl pretreatment can significantly promote the dissolution of cellulose in SFW, and the optimal ultrasonic frequency, solvent and catalyst were 20 + 40 + 60 kHz, [Bmim]Cl and D001-cc resin, respectively; under the best reaction conditions, the maximum 5-HMF yields from the orange and apple wastes were 42.15 and 44.66 mol%, respectively. The kinetic studies showed that the early stage of 100 and 120 °C was mainly the hydrolysis reaction, and late stage was mainly isomerization and dehydration reaction; the early stage of 140 and 160 °C was a rapid hydrolysis and dehydration reaction, and the late stage was mainly the rehydration reaction of 5-HMF. The relationship between the intermediate precursors and 5-HMF showed that the rates of formation and rehydration of 5-HMF increased with the increase in temperature, and the formation reaction was mainly concentrated in zone II. The FT-IR and SEM results of degradation products showed that cellulose in SFW was more easily hydrolyzed at high temperature and long time.

The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the "microbiota-gut-brain" axis. The aims of this study were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundances of commensal microbes in the families Lachnospiraceae and Prevotellaceae, which were significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. Regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolite alteration might be a cofactor for developing of alcohol dependence. IMPORTANCE Gut microbiota dysbiosis is associated with certain psychiatric disorders through the "microbiota-gut-brain" axis. Here, we revealed that alcohol consumption induced colonic microbiota dysbiosis, increased intestinal permeability, and altered the serum metabolic phenotype in rats, and there was a strong correlation between gut microbiota dysbiosis and serum metabolite disorders. Thus, gut microbiota dysbiosis and serum metabolite alteration may be a cofactor for development of alcohol dependence.

The aggregation of amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils, but also facilitates the maintenance of Aβ oligomers on liposome membranes. We structurally characterize the Aβ oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the Aβ ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of Aβ oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.

Background Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice. Methods We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715). Results Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07–3.69, P = 0.03) and neutrophil–lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00–7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%). Conclusion The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

Summary The preparation of flawless and defect-free mixed matrix membranes (MMMs) comprising metal-organic framework (MOF) and polymer is often difficult owing to the poor MOF/polymer interface compatibility. Herein, we present the synthesis of an important family of pillared-layered MOFs with polymerizable moieties based on the parent structure [Zn2L2P]n [L = vinyl containing benzenedicarboxylic acid linkers; P = 4,4′-bipyridine (bipy)]. The crystalline structures of polymerizable MOFs were analyzed using single-crystal X-ray crystallography. The presence of reactive double bonds in MOFs was verified by the successful thiol-ene click reaction with sulfhydryl compounds. The subsequent copolymerization of polymerizable MOFs with organic monomers produced mixed matrix membranes with enhanced MOF/polymer interfacial adhesion that enabled good separation efficiency of CO2 from flue gas. This strategy provides a stimulating platform to the preparation of highly efficient MMMs that are capable of mitigating energy consumption and environment issues., Graphical abstract, Highlights • A new class of vinyl-containing MOFs was constructed for the separation of CO2 and N2. • The structure of BUCT MOFs were analyzed by single-crystal X-ray crystallography. • The C=C double bonds of BUCT MOFs can serve as polymerizable groups with high activity. • BUCT-2 based MMM exhibited a superior CO2/N2 selectivity of 41.6.

Detrimental lithium polysulfide (LiPS) shuttle effects and sluggish electrochemical conversion kinetics in lithium-sulfur (Li-S) batteries severely hinder their practical application. Separator modification has been extensively investigated as an effective strategy to address above issues. Nevertheless, in the case of functional separators, how to effectively block the LiPSs from diffusion while enabling the rapid Li ion transport remains a challenge. Herein, by using an "oxidation-etching" method, MXene membranes are presented with controllable in-plane pores as interlayer to regulate Li ion transportation and LiPS immobilization. Porous MXene membranes with optimized pore density and size can simultaneously anchor LiPS and ensure fast Li ion diffusion. Consequently, even with pure sulfur cathode, the improved Li-S batteries deliver excellent rate performance up to 2 C with a reversible capacity of 677.6 mAh g-1 and long-term cyclability over 500 cycles at 1 C with a low capacity decay of 0.07% per cycle. This work sheds new insights into the design of high-performance interlayers with manipulated nanochannels and tailored surface chemistry to regulate LiPSs trapping and Li ion diffusion in Li-S batteries.

Hydrolyzed polyacrylamide (HPAM) is the most widely used water-soluble linear polymer with high molecular weight in polymer flooding. Microbiological degradation is an environment-friendly and effective method of treating HPAM-containing oilfield produced water. In this study, a strain SZK-5 that could degrade HPAM was isolated from soil contaminated by oilfield produced water. Based on morphological, biochemical characteristics and 16S rDNA sequence homology analysis, the strain was identified as Bacillus megaterium. The biodegradation capability of strain SZK-5 was determined by incubation in a mineral salt medium (MSM) containing HPAM under different environmental conditions, showing 55.93% of the HPAM removed after 7 d of incubation under the optimum conditions ((NH4)2SO4 = 1667.9 mg L−1, temperature = 24.05 °C and pH = 8.19). Cytochrome P450 (CYP) and urease (URE) played significant roles in biological carbon and nitrogen removal, respectively. The strain SZK-5 could resist the damages caused by oxidative stress given by crude oil and HPAM. To our knowledge, this is the first report about the biodegradation of HPAM by B. megaterium. These results suggest that strain SZK-5 might be a new auxiliary microbiological resource for the biodegradation of HPAM residue in wastewater and soil.

Obesity is prone to cause a variety of chronic metabolic diseases, and it has aroused people's attention that the rapid increase in the global population of obese people in the past years. As a kind of weight-loss drug acting in the intestine, lipase inhibitor does not enter the bloodstream without producing central nervous side effects. Because they do not affect the metabolism system, lipase inhibitors and obesity have become one of the hot spots in recent years. Glycolic acid is a new substrate analog inhibitor with the value of the semi-inhibitory concentration of lipase is estimated to be 17.29 ± 0.14 mM. Using the plots of Lineweaver-Burk, the inhibition mechanism of lipase by glycolic acid was reversible and the inhibition type belongs to competitive inhibition with a

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague–Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1β, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p

Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice.OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression.Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group.Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

The accumulation of strontium (Sr) in lettuce and radish under 0 (control), 0.5, 1, 2.5, 5, and 10 mM Sr treatments in hydroponic solution at 16, 23 and 30 days and the effects of Sr stress on six nutrient elements in plants were investigated. The results showed that Sr concentrations in plant aerial and underground parts increased in low-Sr treatments (0.5, 1 and 2.5 mM) and fluctuated in high-Sr treatments (5 and 10 mM) throughout the three sampling periods. Sr concentrations were higher in roots than in leaves, reaching 108.8 ± 14.7 and 134.1 ± 1.2 mg/g in lettuce and radish roots, respectively, after 10 mM Sr treatment. Translocation factor (TF) values (ratio of the Sr concentrations in aerial parts to that in roots) were inversely related to the Sr content in the hydroponic solution, and reached 1.45 ± 0.17 to 0.15 ± 0.03 and 1.06 ± 0.20 to 0.12 ± 0.004 for lettuce and radish. The variation in chlorophyll content was consistent with that in plant biomass.

The crystallization behavior of glass-ceramic seals for solid oxide fuel cells (SOFC) applications was investigated using thermal analysis. Two kinds of glass-based seals H1-20 and H4-20 were formulated by adding 20 wt% YSZ (Y2O3 stabilized ZrO2) powder into two powdered glasses H1 and H4. The results showed that the two seals can inhibit uncontrolled deformation and maintain structure integrity at SOFC operation temperatures. The Avrami parameters (n) calculated for the seals H1-20 and H4-20 are 3.2 and 2.6, respectively, and the respective activation energies (Ec) of crystal growth calculated are 17.2 kJ/mol and 32.7 kJ/mol. These crystallization kinetic parameters are consistent with the results of the phase transformation analyses for the two seals at 750 °C, suggesting that the thermal stability of the seal H4-20 was higher than that of the seal H1-20. Furthermore, the microstructure of the two seals were characterized using XRD and TEM, and the results suggest that the seal H4-20 is a promising candidate for long-term SOFC stack applications.

Dense ceramic mixed ionic-electronic conducting membranes (MIECMs) are renowned for their rich and varied properties as admirable candidates in energy industries, such as oxygen separation from air, cathode materials for solid fuel oxide cells (SOFCs) or membrane reactors for partial oxidation of light hydrocarbons. Especially, the MIECMs integrated oxy-fuel combustion is considered to be a promising cost-effective and efficient method for CO2 capture and sequestration. During the oxy-fuel process, high purity oxygen production has been put forward to use OTMs technology instead of the conventional cryogenic technique, which can benefit from low costs and energy consumption and high efficiency. According to the phase numbers, the OTMs can be classified into single phase and composite OTMs. Extensive research activities have been directed towards the single phase perovskite-type oxides due to their high oxygen permeability. However, their industrial practical application was limited since they suffer from deactivation in the presence of CO2 due to alkaline earth carbonates forming on their surfaces. In order to overcome these issues, focus has shifted to the development of dual-phase membranes consisting of an oxygen ion conducting phase and an electron ion conducting phase, which benefit from the contribution of each phase and overcome the limitations of perovskite materials. Dual-phase OTM typically composed of an oxygen conducting phase (OCP) and an electronic conducting phase (ECP), which displays a better structural and mechanical stability comparing with the single phase OTM under reducing atmosphere due to the incorporation of fluorite phase. The first generation dual-phase OTMs are usually made from the fluorite oxides and noble metals, where fluorite oxides are used as the OCP and noble metals are adopted as the ECP. However, the noble metal-containing dual-phase OTM is too expensive. In order to lower the costs, researchers have developd the second generation dual-phase OTMs, which are consisted of fluorite oxides and perovskite oxides. Although the costs have been reduced, reactions between two phases were usually observed in the second generation dual-phase OTMs. Based on the previous findings and driven by the demands for oxy-fuel combustion for CO2 capture, research put forwards to the new CO2-stable dual-phase OTMs without noble metals and alkaline earth elements. Until now, already a large number of CO2-stable dual-phase membrane materials have been explored. However, their CO2 stabilities have been enhanced, but most of their oxygen permeabilities are too low for practical applications. Therefore, continues research efforts have to be made since most of available OTMs materials can′t satisfy the practical applications. In order to enhance the oxygen permeability and/or improve material thermochemical stability of dual-phase OTMs, the large majority of studies focused on tuning the composition through doping, synthesized temperatures, modified the membrane surfaces with coating or development of new synthesis methods. Meanwhile, considerable theoretical efforts have been put into the dual-phase OTMs, a number of models for permeation process such as Bouwmeester model, Xu-Thomson model, and Zhu model et al. are proposed. Up to now, countless publications has been produced in this field. In order to give the guidelines for the development of the dual-phase OTM materials and promote the process of industrialization of the OTMs technology in the oxy-fuel process, we summarize the status of CO2-stable dual-phase mixed conductor oxygen permeable membrane materials. In this review, the oxygen permeability mechanism and research progress of the dual-phase OTM materials are briefly introduced firstly. Subsequently, the influence of the preparation methods, sintering temperatures, ratios of two phases and the composition of the two phases on the oxygen permeability and stability are analyzed systematically. Next, the applications of dual phase MIECM reactor in partial oxidation of methane to syngas (POM), coupling reactions, water decomposition and oxy-fuel combustion are introduced and analyzed. Finally, the existing scientific problems and the possible research directions have been pointed out.

Purpose: Retinoic acid α (RARα) is overexpressed in various tumors and facilitates cancer progression. Although RARα has been shown to facilitate colorectal cancer (CRC) progression, more efforts to characterize mechanisms of RARα in CRC are needed in order to develop better target-based drugs for tumor therapy. Methods: RARα expression in CRC was assessed by IHC. EdU, QPCR, Western blotting, dual-luciferase reporter assay and ChIP were performed to explore the role of RARα in CRC and the mechanism involoved. Results: Here, we show an overexpression of RARα in 73.5% (i.e., 25 of 34 human CRC specimens). RARα knockdown decreased cell proliferation, migration, and invasion. Such phenotypic manifestations can be correlated to lowered activation of Akt and expression of PCNA (proliferating cell nuclear antigen) as well as MMP2 (matrix metallopeptidase). Mechanistically, RARα facilitates CRC growth through Akt signaling activation to cause levels of PCNA to be upregulated. Furthermore, RARα promotes migration and invasion of CRC cells by directly recruiting the MMP2 promoter to enhance the expression of MMP2. Conclusions: These findings demonstrate that CRC carcinogenesis is promoted by RARα via an enhanced Akt signaling and by increasing MMP2 transcription. CRC therapy can examine the use of RARα as a prospective molecular target.

Increasing molecular π-conjugation length generally improves the light-harvesting ability and enhancing π-π stacking interactions could improve the charge-carrier transport ability in small molecules (SMs). Both are beneficial for increasing power conversion efficiencies (PCEs) in organic solar cells. In this work, two linear (A−D)2Ar-type SMs of (DTBT-TPA)2An and (DPP-TPA)2An were designed and synthesized, in which 4,7-di(thiophen-2-yl)benzothiadiazole (DTBT) and diketopyrrolopyrrole (DPP) were selected as electron acceptors (A), triphenylamine (TPA) was used as electron donor (D) and 9,10-anthracene (An) was used as π-bridge (Ar group), respectively. For comparison, two D−A-type SMs of DTBT-TPA and DPP-TPA were also prepared without anthracene unit. By systematically comparing their optical and electronic properties, it was found that (A−D)2Ar-type SMs show stronger photo response with higher absorption coefficients than the D−A-type counterparts. And introducing anthracene unit could slightly lower their HOMOs of the resulting (A−D)2Ar-type SMs. In bulk heterojunction solar cells, PCEs of 1.72% and 1.36% were achieved in (DTBT-TPA)2An and (DPP-TPA)2An based devices without any solvent additive, which are about 1.5 and 1.9 times the corresponding values of the DTBT-TPA and DPP-TPA based devices, respectively.

In this paper, a tunable acid-resistant Zr-doped indium oxide (ZrInO) semiconductor material was developed. Detailed studies showed that the acid resistance of ZrInO thin films is tunable and increases with the increase in annealing temperature. Taking advantage of this special property, we successfully fabricated back-channel-etched (BCE) thin-film transistors (TFTs) based on the tunable acid-resistant ZrInO thin film. ZrInO-TFTs with BCE structure exhibited excellent electrical performance with a saturation mobility of 21.4 cm $^{\textsf {2}}\textsf {V}^{-\textsf {1}}\textsf {s}^{-\textsf {1}}$ , a subthreshold swing of 0.28 V/decade, and an ON/OFF current ratio of $1.0\times107$ . These results envision that the developed ZrInO semiconductor with tunable acid resistance has a good prospect for the channel layer of BCE-TFTs.