Candida tropicalis oligopeptide transporters assist in the transmembrane transport of the antimicrobial peptide CGA-N9.

Candida tropicalis is often reported as the second or third most common pathogen causing fungal infections. Antimicrobial peptides (AMPs) have attracted increasing attention for their broad-spectrum antimicrobial properties and low cytotoxicity. Our previous studies have shown that CGA-N9, a non-membrane-rupturing AMP, crosses the cell membrane to exert anticandidal activity. We speculate that there are some related transporters that assist in the transmembrane transport of CGA-N9. In this study, the relationship between CGA-N9 lethality kinetics and its real-time transmembrane amount in C. tropicalis cells was investigated. The results demonstrated that there was a positive correlation between its candicidal activity and transmembrane amount. A total of 12 oligopeptide transporter (OPT) coding sequences (CDSs) were cloned from C. tropicalis by using the conservative OPT gene sequences of Candida spp. to design primers and were named C. tropicalis OPTs (CtOPTs). The results of RT‒qPCR demonstrated that the expression levels of CtOPT1, CtOPT9 and CtOPT12 were correlated with the CGA-N9 transmembrane amount in a time-dependent manner. The results of molecular docking demonstrated that CtOPT1, CtOPT9 and CtOPT12 interact strongly with CGA-N9. Therefore, CtOPT1, CtOPT9 and CtOPT12 were predicted to assist in the transmembrane transport of the AMP CGA-N9.

Activities of a broad-spectrum antimicrobial peptide analogue SAMP-A4-C8 and its combat against pneumonia in Staphylococcus aureus-infected mice.

Antimicrobial peptides and their analogues have become substitutes for antibiotics in recent years. The antimicrobial peptide analogue SAMP-A4-C8 (n-octanoic-VRLLRRRI) with high antimicrobial activity was found in our lab. We speculate that it may kill pathogens by some lethal mechanism of action. In the present investigation, the microbicidal activities of SAMP-A4-C8 and its mechanism of action were investigated. The results demonstrated that SAMP-A4-C8 had lethal activities against Staphylococcus aureus and Candida albicans by cell disruption. Based on its microbicidal activities, we believe that it is worth further research for its potential as drug candidate. The results showed that SAMP-A4-C8, with low propensity to induce the resistance of S. aureus and C. albicans, could kill the persister cells of S. aureus and C. albicans, exhibited biofilm forming inhibition activity and preformed biofilm eradication ability against S. aureus and C. albicans, and displayed therapeutic potential on pneumonia in S. aureus-infected mice by reducing lung inflammation. The present study provided a promising drug candidate in the war against multidrug resistance.

Metal-organic framework-modulated Fe3O4 composite au nanoparticles for antibacterial wound healing via synergistic peroxidase-like nanozymatic catalysis.

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

One-Dimensional Co-Carbonate Hydroxide@Ni-MOFs Composite with Super Uniform Core-Shell Heterostructure for Ultrahigh Rate Performance Supercapacitor Electrode.

The insufficient contact between two phases in the heterostructure weakens the coupling interaction effect, which makes it difficult to effectively improve the electrochemical performance. Herein, a Co-carbonate hydroxide@ Ni-metal organic frameworks (Co-CH@Ni-MOFs) composite with super uniform core-shell heterostructure is fabricated by adopting 1D Co-CH nanowires as structuredirecting agents to induce the coating of Ni-MOFs. Both experimental and theoretical calculation results demonstrate that the heterostructure plays a vital role in the high performance of the as-prepared materials. On the one hand, the construction of super uniform core-shell heterostructure can create a large number of interfacial active sites and take advantages of the electrochemical characteristics of each component. On the other hand, the heterostructure can increase the adsorption energy of OH- ions and promote the electrochemical activity for improving the reversible redox reaction kinetics. Based on the aforementioned advantages, the as-fabricated Co-CH@Ni-MOFs electrode exhibits a high specific capacity of 173.1 mAh g-1 (1246 F g-1 ) at 1 A g-1 , an ultrahigh rate capability of 70.3% at 150 A g-1 and excellent cycling stability with 90.1% capacity retention after 10 000 cycles at 10 A g-1 . This study may offer a versatile design for fabricating a MOFs-based heterostructure as energy storage electrodes.

PXR mediates mifepristone-induced hepatomegaly in mice.

Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing's syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr-knockout mice. The results demonstrated that high-dose Mif (100 mg · kg-1 · d-1, i.p.) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg-1 · d-1, i.p.) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg-1 · d-1, i.p.) failed to induce hepatomegaly in Pxr-knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.

Natural product-based screening led to the discovery of a novel PXR agonist with anti-cholestasis activity.

Cholestasis is a major cause of a series of bile flow malfunction-related liver diseases. Pregnane X receptor (PXR) is a key regulator in endo- and xeno-biotics metabolism, which has been considered as a promising therapeutic target for cholestasis. In this study we conducted human PXR (hPXR) agonistic screening using dual-luciferase reporter gene assays, which led to discovering a series of potent hPXR agonists from a small Euphorbiaceae diterpenoid library, containing 35 structurally diverse diterpenoids with eight different skeleton types. The most active compound 6, a lathyrane diterpenoid (5/11/3 ring system), dose-dependently activated hPXR with a high selectivity, and significantly upregulated the expression of hPXR downstream genes CYP3A4 and UGT1A1. In LCA-induced cholestasis mouse model, administration of compound 6 (50 mg· kg-1. d-1, ip) for 7 days significantly suppressed liver necrosis and decreased serum levels of AST, ALT, Tbili, ALP, and TBA, ameliorating LCA-induced cholestatic liver injury. We further revealed that compound 6 exerted its anti-cholestatic efficacy via activation of PXR pathway, accelerating the detoxification of toxic BAs and promoting liver regeneration. These results suggest that lathyrane diterpenoids may serve as a promising scaffold for future development of anti-cholestasis drugs.

Characterization and Antioxidant Activity of Mannans from Saccharomyces cerevisiae with Different Molecular Weight.

Polysaccharides were extracted from natural sources with various biological activities, which are strongly influenced by their chemical structure and molecular weight. In this research, mannans polysaccharides were obtained from Saccharomyces cerevisiae by ethanol precipitation. The molecular weight of YM50, YM70, and YM90 mannans was 172.90 kDa, 87.09 kDa, and 54.05 kDa, respectively. Scanning electron microscopy of YM 90 mannans showed a rough surface with numerous cavities, while the surfaces of YM50 and YM70 were relatively smooth. Sepharose CL-6B and FTIR indicated that mannans had the characteristic bands of polysaccharides. The antioxidant activities of polysaccharides were evaluated in vitro using various assays. Mannans showed a good scavenging activity of DPPH radicals which depend on the molecular weight and concentration, and a higher scavenging activity of hydroxyl radical than ferric-reducing power activities. For the three types of mannans, cytotoxicity and hemolytic activity were rarely detected in mice erythrocytes and Caco-2 cells. Those results could contribute to the further application of mannans from Saccharomyces cerevisiae in the food and medicine industry.

Carnitine palmitoyltransferase 1C reverses cellular senescence of MRC-5 fibroblasts via regulating lipid accumulation and mitochondrial function.

Cellular senescence, a state of growth arrest, is involved in various age-related diseases. We previously found that carnitine palmitoyltransferase 1C (CPT1C) is a key regulator of cancer cell proliferation and senescence, but it is unclear whether CPT1C plays a similar role in normal cells. Therefore, this study aimed to investigate the role of CPT1C in cellular proliferation and senescence of human embryonic lung MRC-5 fibroblasts and the involved mechanisms. The results showed that CPT1C could reverse the cellular senescence of MRC-5 fibroblasts, as evidenced by reduced senescence-associated ß-galactosidase activity, downregulated messenger RNA (mRNA) expression of senescence-associated secretory phenotype factors, and enhanced bromodeoxyuridine incorporation. Lipidomics analysis further revealed that CPT1C gain-of-function reduced lipid accumulation and reversed abnormal metabolic reprogramming of lipids in late MRC-5 cells. Oil Red O staining and Nile red fluorescence also indicated significant reduction of lipid accumulation after CPT1C gain-of-function. Consequently, CPT1C gain-of-function significantly reversed mitochondrial dysfunction, as evaluated by increased adenosine triphosphate synthesis and mitochondrial transmembrane potential, decreased radical oxygen species, upregulated respiratory capacity and mRNA expression of genes related to mitochondrial function. In summary, CPT1C plays a vital role in MRC-5 cellular proliferation and can reverse MRC-5 cellular senescence through the regulation of lipid metabolism and mitochondrial function, which supports the role of CPT1C as a novel target for intervention into cellular proliferation and senescence and suggests CPT1C as a new strategy for antiaging.

Dexamethasone-Induced Liver Enlargement Is Related to PXR/YAP Activation and Lipid Accumulation but Not Hepatocyte Proliferation.

Dexamethasone (Dex), a widely prescribed anti-inflammatory drug, was reported to induce liver enlargement (hepatomegaly) in clinical practice and in animal models. However, the underlying mechanisms are not elucidated. Dex is a known activator of pregnane X receptor (PXR). Yes-associated protein (YAP) has been implicated in chemically induced liver enlargement. Here, the roles of PXR and YAP pathways were investigated in Dex-induced hepatomegaly. Upregulation of PXR downstream proteins, including cytochrome P450 (CYP) 3A11, 2B10, and organic anion transporter polypeptide 2 (OATP2), indicated PXR signaling was activated after high dose of Dex (50 mg/kg, i.p.), and Dex at 100 µM activated PXR in the dual-luciferase reporter gene assay. Dex also increased the expression of total YAP, nuclear YAP, and YAP downstream proteins, including connective tissue growth factor and cysteine-rich angiogenic inducer 61, indicating activation of the YAP pathway. Furthermore, nuclear translocation of YAP was promoted by activation of PXR. However, hepatocyte proliferation was inhibited with significant decrease in the expression of proliferation-related proteins cyclin D1 and proliferating cell nuclear antigen as well as other regulatory factors, such as forkhead box protein M1, c-MYC, and epidermal growth factor receptor. The inhibitory effect of Dex on hepatocyte proliferation was likely due to its anti-inflammation effect of suppression of inflammation factors. ß-catenin staining revealed enlarged hepatocytes, which were mostly attributable to the accumulation of lipids, such as triglycerides. In summary, high-dose Dex increased liver size accompanied by enlarged hepatocytes, and this was due to the activation of PXR/YAP and their effects on lipid accumulation but not hepatocyte proliferation. These findings provide new insights for understanding the mechanism of Dex-induced hepatomegaly. SIGNIFICANCE STATEMENT: This study identified the roles of pregnane X receptor (PXR) and yes-associated protein (YAP) pathways in dexamethasone (Dex)-induced hepatomegaly. Dex induced PXR/YAP activation, enlarged hepatocytes, and promoted liver enlargement with lipid accumulation, such as triglycerides. However, hepatocyte proliferation was inhibited by the anti-inflammatory effect of Dex. These findings provide new insights for understanding the mechanism of Dex-induced hepatomegaly.

Fabrication of novel MXene (Ti3C2)/polyacrylamide nanocomposite hydrogels with enhanced mechanical and drug release properties.

A highly stretchable nanocomposite (NC) hydrogel was fabricated via in situ free radical polymerization of acrylamide. In particular, an exfoliated two-dimensional MXene (Ti3C2) nanosheet was utilized as a crosslinker instead of traditional organic crosslinkers. The exfoliated Ti3C2 nanosheets were confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS) measurements. Compared with traditional organic crosslinked N,N-methylene bisacrylamide (BIS)/polyacrylamide (PAM) hydrogels (fracture strength of 32.0 kPa and elongation of 109.6%), the synthesized Ti3C2/PAM NC hydrogels exhibited greatly improved mechanical properties with fracture strengths of 66.5 to 102.7 kPa, compressive strengths of 400.6 to 819.4 kPa and elongations at break of 2158.6% to 3047.5% as the Ti3C2 content increases from 0.0145% to 0.0436%. The enhanced mechanical performances can be attributed to the honeycomb-like fine structure with uniform pores as well as more flexible polymer chains in NC hydrogel networks. When loaded with drugs, Ti3C2/PAM NC hydrogels exhibited good sustained-release performance, higher drug loading amounts (97.5-127.7 mg g-1) and higher percentage releases (62.1-81.4%), greatly superior to those of the BIS/PAM hydrogel (46.4 mg g-1, 45.0%). Our work reveals the application of MXene materials in the fabrication of NC hydrogels with enhanced mechanical and drug release behaviors.

Activity and mechanism of action of antimicrobial peptide ACPs against Candida albicans.

AIMS: Candida albicans is the most prevalent pathogenic fungus, exhibiting escalating multidrug resistance (MDR). Antimicrobial peptides (AMPs) represent promising candidates for addressing this issue. In this research, five antimicrobial peptides, ACP1 to ACP5 which named ACPs were studied as alternative fungicidal molecules. MAIN METHODS: CD assay was used to analyze the 2D structures, Absorbance method was used to test the antimicrobial activity, haemolytic activity, time-kill kinetics, biofilm inhibition and reduction activity, resistance induction activity and assessment against fluconazole-resistant C. albicans. SEM, TEM, CLSM, flow cytometer and FM were carried out to provide insight into the mechanisms of anti-Candida action. KEY FINDINGS: ACPs possessed an α-helical structure and strong anti-Candida activities, with minimum inhibitory concentrations (MICs) from 3.9 to 15.6 µg/mL. In addition, ACPs did not produce hemolysis at concentrations lower than 10 or 62 × MIC, indicating their low cytotoxicity. Fungicidal kinetics showed that they completely killed C. albicans within 8 h at 2 to 4 × MIC. Notably, ACPs were highly fungicidal against fluconazole-resistant C. albicans and showed low resistance. In addition, they were effective in inhibiting mycelium and biofilm formation. Fluorescence microscopy revealed that while fluconazole had minimal to no inhibitory effect on biofilm-forming cells, ACPs induced apoptosis in all of them. The research on mechanism of action revealed that ACPs disrupted the cell membranes, with ROS increasing and cellular mitochondrial membrane potential decreasing. SIGNIFICANCE: ACPs could be promising candidates for combating fluconazole-resistant C. albicans infections.

Efficient collection of excitation energy from a linear-shaped weakly interacted perylenetetracarboxylic diimides array.

A series of novel light-harvesting compounds (namely PO-PN, PO-PO-PN and PO-PO-PO-PN) were synthesized with a linear-shaped phenoxy group-substituted perylenetetracarboxylic diimide (PO) oligomer as donor and a pyrrolidinyl group-substituted perylenetetracarboxylic diimide (PN) as acceptor. The photophysical properties of these linear-shaped compounds are investigated by steady state electronic absorption, fluorescence spectra and lifetime measurements. The ground state interactions between the neighbor PO subunits within these three compounds are weak. No matter which PO subunit is excited in these linear molecules, the excitation energy is finally collected by the PN subunit. The excitation energy can transfer as long as 47 Å without any decrease in efficiency. The energy transfer rate constants determined by femtosecond transient absorption experiments are fast and close to that of the energy transfer from B800 to B850 in LH II of natural photosynthesis.

Lyoprotectant Formulation and Optimization of the J-Aggregates Astaxanthin/BSA/Chitosan Nanosuspension.

Astaxanthin is a carotenoid with excellent antioxidant activity. However, this small lipid-soluble molecule is insoluble in water and has low stability. Although this situation can be improved when astaxanthin is prepared as a nanosuspension, the aqueous form is still not as convenient and safe as the dry powder form for storage, transport, and use. The lyophilization process provides better protection for thermosensitive materials, but this leads to collapse and agglomeration between nanoparticles. To improve this situation, appropriate lyophilization protectants are needed to offer support between the nanoparticles, such as sugars, amino acids, and hydroxy alcohols. The purpose of this work is to screen lyophilization protectants by single-factor experiments and response surface optimization experiments and then explore the optimal ratio of compound lyophilization protectants, and finally, make excellent astaxanthin/BSA/chitosan nanosuspension (ABC-NPs) lyophilized powder. The work shows that the optimal ratio of the compounding lyophilization protectant is 0.46% oligomeric mannose, 0.44% maltose, and 0.05% sorbitol (w/v). The ABC-NPs lyophilized powder prepared under the above conditions had a re-soluble particle size of 472 nm, with a ratio of 1.32 to the particle size of the sample before lyophilization. The lyophilized powder was all in the form of a pink layer. The sample was fluffy and dissolved entirely within 10 s by shaking with water. Consequently, it is expected to solve the problem of inconvenient storage and transportation of aqueous drugs and to expand the application of nanomedicine powders and tablets.

Synergistic Pro-Apoptotic Effect of a Cyclic RGD Peptide-Conjugated Magnetic Mesoporous Therapeutic Nanosystem on Hepatocellular Carcinoma HepG2 Cells.

Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGDSPIO@MSN NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the prepared RGDSPIO@MSN NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that the RGDSPIO@MSN@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma.

Anti-CD44 antibodies grafted immunoaffinity Fe3O4@MnO2 nanozymes with highly oxidase-like catalytic activity for specific detection of triple-negative breast cancer MDA-MB-231 cells.

Cell-enzyme-linked immunosorbent assay (CELISA) is extensively applied for cancer diagnosis and screening because of its simple operation, high sensitivity, and intuitive color change. However, the unstable horseradish peroxidase (HRP), hydrogen peroxide (H2O2) and non-specificity have led to a high false negative rate, which limits its application. In this study, we have developed an innovative immunoaffinity nanozyme aided CELISA based on anti-CD44 monoclonal antibodies (mAbs) bioconjugated manganese dioxide-modified magnetite nanoparticles (Fe3O4@MnO2 NPs) for the specific detection of triple-negative breast cancer MDA-MB-231 cells. The CD44FM nanozymes were fabricated to replace unstable HRP and H2O2 to counteract possible negative effects in conventional CELISA. Results suggested that CD44FM nanozymes displayed remarkable oxidase-like activities over an extensive pH and temperature range. The bioconjugation of CD44 mAbs enabled CD44FM nanozymes to enter MDA-MB-231 cells selectively via over-expressed CD44 antigens on the membrane surface of these cells, and then catalyzed oxidation of the chromogenic substrate TMB, further achieving specific detection of these cells. Additionally, this study exhibited high sensitivity and low detection limit for MDA-MB-231 cells with a quantitation range of just 186 cells. To sum up, this report developed a simple, specific and sensitive assay platform based on CD44FM nanozymes, which could provide a promising strategy for targeted diagnosis and screening of breast cancer.

A Dual-Mechanism Based Nutrient Partitioning Nanoregulator for Enhanced Immunotherapy against Anti-PD-1 Resistant Tumors.

Competitive consumption of nutrients between rapidly proliferating cancer cells and T cells results in an immunosuppressive tumor microenvironment (TME) and nutrient deprivation of T cells, which can cause low response rate and resistance to immunotherapies. In this study, we proposed a dual-mechanism based nutrient partitioning nanoregulator (designated as DMNPN), which can simultaneously regulate the immunosuppressive TME and enhance T cell nutrient availability. DMNPN consists of a charge-reversal biodegradable mesoporous silica, encapsulating glycolysis inhibitor lonidamine, and small interfering RNA against glutaminase. Through inhibiting glycolysis to decrease the lactic acid production and downregulating glutaminase expression to reduce the uptake of glutamine by tumor cells, DMNPN enables effective remodeling of metabolism and nutrient partitioning, which alleviates the immunosuppressive TME and boosts nutrient availability for T cells with enhanced antitumor immunity. Such a nutrient partitioning nanoregulator can effectively inhibit the growth of anti-programmed death receptor 1 (anti-PD-1) resistant tumors and prevent tumor metastasis and recurrence. Overall, this dual-mechanism based nutrient reallocation strategy provides a promising approach for cancer therapy.

Fabrication and characterization of the H/J-type aggregates astaxanthin/bovine serum albumin/chitosan nanoparticles.

Astaxanthin is a natural liposoluble ketocarotenoid with various biological activities. Hydrophobic astaxanthin with C2h symmetry can self-assembly form H-type aggregates and J-type aggregates in hydrated polar solvents. However, astaxanthin and its aggregates are limited by its water insolubility and chemical instability. Here, the biological macromolecules bovine serum albumin (BSA) and chitosan were chosen as protein-polysaccharides based delivery systems for astaxanthin aggregates by molecular self-assembly method. The precise prepared H-ABC-NPs and J-ABC-NPs suspensions were both near spheres with hydrodynamic size around 281 ± 9 nm and 368 ± 5 nm and zeta potentials around +26 mV and +30 mV, respectively. Two types of astaxanthin aggregates were distinguished, water-dispersible, and stable in nanocarriers through UV-vis spectra observation. The encapsulation efficiency of the astaxanthin in ABC-NPs was above 90 %. Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) analyses indicated that the dominant driving forces of ABC-NPs formation mainly included electrostatic, hydrophobic interactions and hydrogen bonding. These results offer an elegant opportunity for the protein-polysaccharides delivery systems, and provide an important perspective for applying novel water-dispersed astaxanthin aggregates products in nutrition and medicine industry.

Nanosheet-assembled NiCo-LDH hollow spheres as high-performance electrodes for supercapacitors.

Layered double hydroxides (LDHs) have been considered as favorable pseudocapacitive electrode materials for supercapacitors due to their tunable layered structure/compositions and low cost. Here, we report the NiCo-LDH hollow spheres prepared with Co-glycerate as the sacrificial template and cobalt source. The hollow spheres are assembled with frizzy NiCo-LDH nanosheets, where the hollow structure can inhibit agglomeration of the LDH nanosheets to expose more active sites and shorten the diffusion path of electrolyte ions. The prepared NiCo-LDH hollow spheres show a high specific capacitance of 1962 F g-1 at 1 A g-1 and good capacitance retention rate of 66.4 % at 30 A g-1. The asymmetric supercapacitors fabricated using NiCo-LDH hollow spheres as positive electrode yields a large energy density 62.9 Wh kg-1 at the power density of 0.8 kW kg-1. This research may develop a facile synthesis way to prepare LDH hollow spheres for supercapacitors.

MXenes induced formation of Ni-MOF microbelts for high-performance supercapacitors.

For the sake of developing new energy storage devices for satisfying the energy needs of the modern society, we herein report an innovative MXene-induced strategy to synthesize Ti3C2Tx MXenes/Ni based metal-organic framework composites (Ti3C2Tx/Ni-MOFs) for high-performance supercapacitors. The two-dimensional (2D) MXenes with oxygen-containing groups on the surface can be used as structure-directing agents to tune the Ni-MOFs into 2D microbelts. The presence of MXenes cannot only improve conductivity of the composite but also provide additional electric double layer capacitance and faradaic pseudocapacitance. The 2D Ni-MOF microbelts can offer rich activity sites for the faradaic redox reactions and shorten the ion transport path. Taking advantages of synergistic effects of Ni-MOF microbelts and Ti3C2Tx MXenes, the prepared Ti3C2Tx/Ni-MOFs electrode shows a good electrochemical performance with 1124 F g-1 at the current density of 1 A g -1 and 62% rate capability at 20 A g -1. This work can offer a new insight to design 2D MOF belts as high-performance electrode materials for supercapacitors.

Lathyrane Diterpenoids as Novel hPXR Agonists: Isolation, Structural Modification, and Structure-Activity Relationships.

Pregnane X receptor (PXR) that orchestrates the intricate network of xeno- and endobiotic metabolism is considered as a promising therapeutic target for cholestasis. In this study, the human PXR (hPXR) agonistic bioassay-guided isolation of Euphorbia lathyris followed by the structural modification led to the construction of a lathyrane diterpenoid library (1-34). Subsequent assay of this library led to the identification of a series of potent hPXR agonists, showing better efficacy than that of typical hPXR agonist, rifampicin. The most active compound, 8, could dose-dependently activate hPXR at micromolar concentrations and significantly up-regulate the expressions of PXR downstream genes CYP3A4, CYP2B6, and MDR1. The structure-activity relationships (SARs) studied in combination with molecular modeling suggested that acyloxy at C-7 and the presence of 14-carbonyl were essential to the activity. These findings suggested that lathyrane diterpenoids could serve as a new type of hPXR agonist for future anticholestasis drug development.