In situ Gel Electrolytes for the Interfacial Regulation of Lithium Metal Batteries.

With the popularity and development of electronic devices, the demand for lithium batteries is increasing, which also puts high demands on the energy density, cycle life and safety of lithium batteries. Gel electrolytes achieve both of these requirements by curing the electrolytes to reduce the interfacial side reactions of lithium metal batteries. The ionic conductivity of the gel electrolytes prepared by in situ curing reach 8.0×10-4  S cm-1 , and the ionic mobility number is 0.53. Meanwhile, the gel electrolytes maintain a stable electrochemical window of 1.0-5.0 V. Benefited with the interfacial regulation of PEGDA gel electrolytes, the gel lithium metal batteries show better cycling stability, and achieved 97 % capacity retention after 200 cycles (0.2 C) with a lower increasing rate of impedance.

Near-Infrared Light-Activatable Dual-Action Nanoparticle Combats the Established Biofilms of Methicillin-Resistant Staphylococcus aureus and Its Accompanying Inflammation.

Clinically, inhibition of both bacterial infection and excessive inflammation is a crucial step for improved wound treatments. Herein, the fabrication of near-infrared-light (NIR)-activatable deoxyribonuclease (DNase)-carbon monoxide (CO)@mesoporous polydopamine nanoparticles (MPDA NPs) is demonstrated for efficient elimination of methicillin-resistant Staphylococcus aureus (MRSA) biofilms and the following anti-inflammatory activity. Specifically, thermosensitive CO-gas-releasing donors (CO releasing molecules, FeCO) are first encapsulated into MPDA NPs, followed by covalently immobilizing deoxyribonuclease I (DNase I) on the surfaces of MPDA NPs. DNase I can degrade the extracellular DNA in biofilms, which site specifically destroys the compactness of the biofilms. With NIR irradiation, DNase-CO@MPDA NPs display great photothermal ability, and further trigger on-demand delivery of bactericidal CO gas that can adequately permeate the impaired biofilms. Eventually, they achieve effective MRSA biofilm elimination in virtue of the synergistic effects of both DNase I participation and CO-gas-potentiated photothermal therapy. Importantly, the inflammatory responses of DNase-CO@MPDA NPs and NIR-treated wounds are simultaneously alleviated owing to the anti-inflammatory features of released CO. Finally, NIR-activatable DNase-CO@MPDA NPs accelerate the healing process of MRSA-biofilm-infected cutaneous wounds. Taken together, this phototherapeutic strategy displays great therapeutic potential in treating the formidable clinical problems caused by MRSA biofilms and the accompanying inflammation.

Calcium Peroxide Nanoparticles-Embedded Coatings on Anti-Inflammatory TiO2 Nanotubes for Bacteria Elimination and Inflammatory Environment Amelioration.

Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting pro-inflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO2 nanotubes. Then synthesized CaO2 nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H2 O2 release from CaO2 NPs. The potential cytotoxicity of CaO2 NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions.

Sanguinarine caused larval lethality and growth inhibition by suppressing energy metabolism in silkworms, Bombyx mori.

Sanguinarine (Sang) is a natural alkaloid and distributed in several plants of Papaveraceae. The antitumor, antioxidant, antimicrobial and anti-inflammatory effects of Sang were extensively reported, but its speciality and mechanism against Lepidoptera insects were still unknown. In this study, detailed toxicological parameters of Sang against silkworms, Bombyx mori (B. mori), were determined by a toxicological test. Then, a nuclear magnetic resonance-based (NMR) metabolomics method was adopted to analyze the changes in hemolymph metabolites of silkworms after feeding Sang. The growth of fourth-instar larvae was significantly ceased by the oral administration of 0.05-0.3% Sang and vast deaths appeared in 0.3% Sang group on Day 4 and Day 5. The quantitative analysis of metabolites indicated that trehalose and citrate levels in hemolymph were increased after 24 h of feeding 0.3% Sang, whereas the concentrations of pyruvate, succinate, malate and fumarate were decreased. In addition, the enzymatic determination and reverse transcription quantitative PCR (RT-qPCR) showed that the trehalase (THL) activity and the transcriptional level of one gene coding THL were uniformly weakened by 0.3% Sang. One of the important mechanisms of Sang against silkworms might be interpreted as follows. Sang impaired trehalose hydrolysis, reduced THL activity and transcription, and led to the inhibition of energy metabolism, consequent antigrowth and high lethality in larvae of B. mori. Our findings offered new insights into the insecticidal effect of Sang from the perspective of energy metabolism and provided the basis for the application of Sang in the control of Lepidoptera pests.

AF1q Mediates Tumor Progression in Colorectal Cancer by Regulating AKT Signaling.

The up-regulation of ALL1-fused gene from chromosome 1q (AF1q) is commonly seen in aggressive hematologic malignancies as well as in several solid tumor tissues. However, its expression and intrinsic function in human colorectal cancer (CRC) remains largely undefined. To explore the role of AF1q in human CRC progression, AF1q expression was analyzed in human CRC tissue samples and CRC cell lines. Clinical specimens revealed that AF1q was up-regulated in human CRC tissues, and that this up-regulation was associated with tumor metastasis and late tumor, lymph node, metastasis (TNM) stage. AF1q knockdown by shRNA inhibited tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro, as well as tumorigenesis and liver metastasis in vivo, whereas these effects were reversed following AF1q overexpression. These AF1q-mediated effects were modulated by the protein kinase B (AKT) signaling pathway, and inhibition of AKT signaling attenuated AF1q-induced tumor promotion. Thus, AF1q contributes to CRC tumorigenesis and progression through the activation of the AKT signaling pathway. AF1q might therefore serve as a promising new target in the treatment of CRC.

Theoretical analysis of electrochemical surface-area loss in supported nanoparticle catalysts.

In polymer electrolyte fuel cells a decrease in catalytic surface-area within the cathode catalyst layer is a critical barrier to commercialization. This loss in catalytic surface-area manifests as a loss in cell voltage and thus power density of the cell. It has been established that potential cycling accelerates the loss in catalytic surface-area yet isolating the contributing mechanisms as well as relating mechanisms to operating conditions is not as straightforward. We approach the issue of surface-area loss deconvolution with a combined experimental, modelling and theoretical framework. The methodology is based on the Lifshitz-Slyozov-Wagner and Smoluchowski theories of particle size distribution evolution. Electrochemical surface-area loss experiments probing upper potential limits of 0.9 and 1.2 V as well as temperatures from 298 to 343 K were analyzed with the model. A dissolution and redeposition mechanism was correlated with the measurements for both upper potential limits; however, at the upper potential limit of 1.2 V, ambiguity between the coagulation and the dissolution and redeposition mechanisms was found. Notwithstanding, the extracted dissolution and redeposition parameters aligned with independent studies on Pt dissolution whereas similar positive comparisons with independent results were unable to be made for the coagulation mechanism.

The impact of digital infrastructure on provincial green innovation efficiency-empirical evidence from China.

In the epoch of the digital economy, technological innovation and energy conservation are significantly facilitated by digital infrastructure, leading to substantial improvements in green innovation efficiency at the provincial level. This study employed the feasible generalized least square (FGLS) method to examine the effects of digital infrastructure on the green innovation efficiency across 30 provinces in the Chinese mainland, utilizing panel data from 2011 to 2020. Additionally, this investigation delves into the intervening role of industrial structure upgrading and the amplifying effects of environmental regulation and human capital on the process. Findings indicate that, to begin with, digital infrastructure contributes to the meaningful enhancement of green innovation efficiency within provinces. Subsequently, the industrial structure upgrading partially mediates the impact of digital infrastructure on the efficiency of provincial green innovation. Lastly, both human capital and environmental regulations amplify the beneficial influence of digital infrastructure on the effectiveness of green innovation at the provincial level. This study provides valuable insights into the mechanisms through which digital infrastructure boosts green innovation efficiency, aiding policymakers in formulating appropriate policies to augment digital infrastructure, thereby promoting provincial green innovation efficiency.

Effects of two celery fibers on the structural properties and digestibility of glutinous rice starch: A comparative study.

The present study focused on the extraction of water-soluble dietary fiber (CSDF) and water-insoluble dietary fiber (CIDF) from celery. It investigated their effects on glutinous rice starch's (GRS) physicochemical, structural, and digestive properties. The results showed that as the addition of the two dietary fibers increased, they compounded with GRS to varying degrees, with the complexing index reaching 69.41 % and 60.81 %, respectively. The rheological results indicated that the two dietary fibers reduced the viscosity of GRS during pasting and inhibited the short-term regrowth of starch. The FTIR and XRD results revealed that the two fibers interacted with GRS through hydrogen bonding, effectively inhibiting starch retrogradation. Furthermore, both fibers increased the pasting temperature of GRS, thus delaying its pasting and exhibiting better thermal stability. Regarding digestibility, the starch gels containing dietary fibers exhibited significantly reduced digestibility, with RS significantly increased by 8.15 % and 8.95 %, respectively. This study provides insights into the interaction between two dietary fibers and GRS during processing. It enriches the theoretical model of dietary fiber-starch interaction and provides a reference for the application development of starch-based functional foods.

Ultrasound-propelled liposome circumvention and siRNA silencing reverse BRAF mutation-arised cancer resistance to trametinib.

BRAF-V600E mutation is regarded as the source of lung cancer resistance to trametinib (Tr), and no solution available for completely addressing this intractable resistance has emerged yet. Herein, the combination of ultrasonic (US) propelled folic acid (FA)-modified liposomes strategy and BRAF-driven gene silencing program is proposed to effectively reverse Tr's resistance to lung cancer. Meanwhile, the prepared cationic nanoliposomes can assist Tr drug and BRAF siRNA to escape lysosome disposal, thereby avoiding Tr drug pumping out or siRNA degradation. More significantly, loaded BRAF siRNA is designed to silence BRAF-V600E mutation genes via modulating BRAF-ERK-pathway and remarkably reverse the PC9R resistance to Tr. Systematic experiments validate that these cooperatively sensitize PC9R cells to Tr and shrink resistant NSCLC in vivo, especially after combining with FA-mediated targeting and US-enhanced permeability that permits more intratumoral accumulations of Tr. Such a biocompatible targeting drug-resistance liberation agent and its underlying design strategy lay a foundation avenue to completely reverse tumor resistance, which is preferable to treat BRAF mutation-arised resistance of various tumors, holding high clinical translation potentials.

Synthesis of quantum-sized ZnO nanoparticles in different medium and their application to NO2 sensors.

Quantum-sized ZnO nanoparticles were synthesized using zinc acetate dihydrate through a sol-gel process in different mediums: water, ethanol and methanol. Three types of modifiers: tetraethyl orthosilicate (TEOS), sodium dodecyl sulfate (SDS) and oleic acid (OA) were added to control the growth of the ZnO nanoparticles and inhibit Ostwald ripening. X-ray Diffraction (XRD) analyses revealed that ZnO have a hexagonal crystal structure, the estimated average crystallite sizes of modified ZnO are in the range of 4.5-10 nm, while the crystallite sizes of non-modified ZnO are large than 20 nm. X-ray photoelectron spectroscopy (XPS) analyses obtained the surface composition and chemical states of the products of ZnO. In this paper, the obtained quantum-sized ZnO nanoparticles as a novel sensing material were used to detect NO2 in environment. The sensing tests indicated that the ZnO based sensors not only have high response to NO2 but also exhibited high selectivity to CO and CH4 at low operating temperature of 290 degrees C.

Efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors: a real-world, multicenter, observational study.

Introduction: Mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor-α (PDGFRA) render the available tyrosine kinase inhibitors (TKI) ineffective in treating advanced gastrointestinal stromal tumors (GIST). Ripretinib, a broad-spectrum switch-control kinase inhibitor, has shown increased efficacy and manageable safety, but real-world evidence remains scarce. This study evaluates the efficacy and safety of ripretinib among Chinese patients in a real-world setting. Methods: Advanced GIST patients (N=23) receiving ripretinib following progression on previous lines of TKI treatment were enrolled to determine the efficacy [progression-free survival (PFS) and overall survival (OS)]. Safety was assessed by the incidence and severity of adverse events (AEs). All statistical analyses were performed using SPSS version 20.0 and a p-value of <0.05 was considered significant. Results: The median PFS (mPFS) of efficacy analysis set (EAS) (N=21) was 7.1 months. mPFS of patients receiving ripretinib following ≤2 lines of previous TKI treatment and ≥3 prior lines of therapy were 7.1 and 9.2 months, respectively. The median OS (mOS) was 12.0 months and shorter interval between the end of the latest TKI and ripretinib therapy was correlated with longer median PFS and OS (p=0.054 and p=0.046), respectively. Alopecia and asthenia were the most common AEs observed. Conclusion: Compared to previous lines of TKI in advanced GIST patients, ripretinib showed superior efficacy with clinically manageable AEs. Real-world results are comparable to that of phase III INVICTUS study and its Chinese bridging study. Hence, ripretinib can be used for the clinical management of advanced GIST patients.

The impact of digital inclusive finance on provincial green development efficiency: empirical evidence from China.

Green development is inseparable from financial support. The impact of digital inclusive finance (DIF), an emerging financial format, on the green development efficiency (GDE) needs to be studied. Using the panel data of the Provincial Digital Financial Inclusion Index from 2011 to 2019, this paper examines the impact of DIF and its coverage breadth (CB), usage depth (UD), and digitalization level (DL) on GDE, and analyzes the regional heterogeneity of the impact of DIF on GDE. The research also explores the mechanism by which DIF affects the efficiency of provincial green development, including the moderating role of environmental regulation (ER) and the mediating role of industrial structure upgrade (ISU). The results show that DIF, UD, and DL can significantly improve provincial GDE, and the effect of coverage breadth is not obvious. From a regional perspective, DIF can promote GDE in the eastern and central regions, whereas it has no obvious effect on the western region. Moreover, ER has played a moderation role in the process of DIF affecting GDE. ISU has played a partial mediation role in the process of DIF affecting GDE. The research conclusions can provide relevant suggestions for the green development of China's provinces.

Surface modification of titanium substrate via combining photothermal therapy and quorum-sensing-inhibition strategy for improving osseointegration and treating biofilm-associated bacterial infection.

Insufficient osseointegration and biofilm-associated bacterial infection are important challenges for clinical application of titanium (Ti)-based implants. Here, we constructed mesoporous polydopamine (MPDA) nanoparticles (NPs) loaded with luteolin (LUT, a quorum sensing inhibitor), which were further coated with the shell of calcium phosphate (CaP) to construct MPDA-LUT@CaP nanosystem. Then, MPDA-LUT@CaP NPs were immobilized on the surface of Ti implants. Under acidic environment of bacterial biofilm-infection, the CaP shell of MPDA-LUT@CaP NPs was rapidly degraded and released LUT, Ca2+ and PO4 3- from the surface of Ti implant. LUT could effectively inhibit and disperse biofilm. Furthermore, under near-infrared irradiation (NIR), the thermotherapy induced by the photothermal conversion effect of MPDA destroyed the integrity of the bacterial membrane, and synergistically led to protein leakage and a decrease in ATP levels. Combined with photothermal therapy (PTT) and quorum-sensing-inhibition strategy, the surface-functionalized Ti substrate had an antibacterial rate of over 95.59% against Staphylococcus aureus and the elimination rate of the formed biofilm was as high as 90.3%, so as to achieve low temperature and efficient treatment of bacterial biofilm infection. More importantly, the modified Ti implant accelerated the growth of cell and the healing process of bone tissue due to the released Ca2+ and PO4 3-. In summary, this work combined PTT with quorum-sensing-inhibition strategy provides a new idea for surface functionalization of implant for achieving effective antibacterial and osseointegration capabilities.

ROS-responsive hydrogel coating modified titanium promotes vascularization and osteointegration of bone defects by orchestrating immunomodulation.

Ideal titanium implants are required to participate in bone repair actively to improve in situ osteointegration. However, the traditional surface functionalization methods of titanium implants are difficult to both achieve the active regulation and long-term stability of bioactive components. Here, a novel functionalized titanium which loaded with thymosin ß4 (Tß4) and covered by a hydrogel coating was designed and evaluated. A strong adhesion between the coating and the titanium substrate was realized by the synergistic action of borate ester bonds and surface topological structure. The hydrogel coating also achieved an in vivo adhesion between implant and tissue through hydrogen bonds and borate bonds. In addition, based on the ROS response property of borate bonds, the implant can release Tß4 in response to the immune reaction of bone healing by regulating the polarization of macrophages, thereby reducing the fibrosis formation around the implant interface and promoting vascularization and osteointegration of bone defects.

[Efficacy and safety of glucocorticoids in addition to intravenous immunoglobulin in the initial treatment of Kawasaki disease: a meta-analysis of randomized trials].

OBJECTIVE: To evaluate the efficacy and safety of glucocorticoids (GC) plus intravenous immunoglobulin (IVIG) in the initial treatment of Kawasaki disease. METHODS: Fourteen electronic databases and 3 Japanese magazines were searched. Randomized controlled trials (RCT) describing the use of GC plus IVIG in the initial treatment of Kawasaki disease in children were collected. The data of methodological quality and trial information were extracted by two independent researchers. Cochrane review methodology was used for assessing the trial quality and efficacy. Each dichotomous outcome was measured in terms of odds risk (OR) while continuous outcomes shown as weighted mean differences (WMD). And a meta-analysis was made with RevMan5.0.23.0 software. RESULTS: A total of 416 cases in 3 trials were included. There were 209 cases in GC + IVIG group and 207 cases in IVIG group. The incidence of coronary artery lesion (CAL) was not different between GC + IVIG and IVIG groups within 1 month or 1 month post-treatment (OR: 0.74, 0.69; 95%CI: 0.23 - 2.40, 0.35 - 1.38; P = 0.62, 0.30]. The fever duration was shorter in GC + IVIG group than that in IVIG group (WMD: -0.93 d, 95%CI: -1.15 - -0.70, P = 0.00). The treatment failure rate was less in GC + IVIG group than IVIG group (9.09% vs 17.48%, OR: 0.49, 95%CI: 0.28 - 0.86, P = 0.01). No difference in adverse events was found between two groups (OR: 0.81, 95%CI: 0.22 - 3.03, P = 0.76). CONCLUSION: There is no evidence to support that GC plus IVIG can further reduce the CAL risk of KD patients. But it may lower the treatment failure rate in KD patients.

Physicochemical and in vitro digestibility properties on complexes of fermented wheat starches with konjac gum.

In this study, the wheat starch with natural fermentation for 72 h was combined with konjac gum (KGM) at different concentrations (0, 0.1, 0.3, 0.5%, w/w), and the changes in physicochemical and digestible characteristics of the complexes were investigated. The results showed that KGM clumped fermented starch (FS) granules together and caused the FS gels to form a close network structure. The addition of KGM significantly decreased the amylose content and swelling power, and reduced peak viscosity, final viscosity, and setback value (SB), which indicated that FS-KGM complexes possessed soft gel structure and could resist the short-term retrogradation. KGM impeded the increase of relative crystallinity, retrogradation enthalpy and gel firmness of FS during storage, suggesting the long-term retrogradation of FS was retarded by KGM. All starch pastes had a weak gel-like structure, and higher storage modulus (G') and loss tangent (tan δ) values obtained after the addition of KGM. In vitro digestion results showed that KGM could slow the hydrolysis of FS, resulting in the increase of slowly digested starch (SDS) and resistant starch (RS). In particularly, the FS-0.3KGM showed the ideal structure, the best anti-retrogradation effected, and slowest the hydrolysis.

1 H NMR-based metabonomic evaluation of the pesticides camptothecin and matrine against larvae of Spodoptera litura.

BACKGROUND: Camptothecin (CPT) and matrine (MAT) have potential as botanical pesticides against several pest species. However, the mechanisms of metabolic and physiological changes in pests induced by CPT and MAT are unknown. In this study, a toxicological test, an NMR-based metabolomic study, an enzymatic test, and an RT quantitative PCR (RT-qPCR) experiment were all conducted to examine the effect of CPT and MAT on Spodoptera litura. RESULTS: CPT (0.5-1%) exerted high toxicity against larvae of S. litura and caused growth stagnation and high mortality of larvae. A variety of metabolites were significantly influenced by 0.5% CPT, including several energy-related metabolites such as trehalose, lactate, succinate, citrate, malate, and fumarate. In contrast, MAT showed low toxicity against larvae and induced almost no changes in hemolymph metabolites of S. litura. Enzymatic tests showed that trehalase activity was significantly decreased in larvae after feeding with 0.5% CPT. RT-qPCR showed that the transcription levels of alanine aminotransferase, malate dehydrogenase, and isocitrate dehydrogenase were decreased while lactate dehydrogenase was increased in the 0.5% CPT-treated group. CONCLUSIONS: These data indicate that one of the important mechanisms of CPT against S. litura larvae is via the inhibition of trehalose hydrolysis and glycolysis. Our findings also suggest that CPT exhibits a stronger toxicological effect than MAT against S. litura, which provides basic information for the application of CPT in the control of S. litura or other lepidoptera pests.

Measures of the Degree of Departure from Ignorable Sample Selection.

With the current focus of survey researchers on "big data" that are not selected by probability sampling, measures of the degree of potential sampling bias arising from this nonrandom selection are sorely needed. Existing indices of this degree of departure from probability sampling, like the R-indicator, are based on functions of the propensity of inclusion in the sample, estimated by modeling the inclusion probability as a function of auxiliary variables. These methods are agnostic about the relationship between the inclusion probability and survey outcomes, which is a crucial feature of the problem. We propose a simple index of degree of departure from ignorable sample selection that corrects this deficiency, which we call the standardized measure of unadjusted bias (SMUB). The index is based on normal pattern-mixture models for nonresponse applied to this sample selection problem and is grounded in the model-based framework of nonignorable selection first proposed in the context of nonresponse by Don Rubin in 1976. The index depends on an inestimable parameter that measures the deviation from selection at random, which ranges between the values zero and one. We propose the use of a central value of this parameter, 0.5, for computing a point index, and computing the values of SMUB at zero and one to provide a range of the index in a sensitivity analysis. We also provide a fully Bayesian approach for computing credible intervals for the SMUB, reflecting uncertainty in the values of all of the input parameters. The proposed methods have been implemented in R and are illustrated using real data from the National Survey of Family Growth.

Proanthocyanidin-Aluminum Complexes Improve Aluminum Resistance and Detoxification of Camellia sinensis.

Aluminum (Al) influences crop yield in acidic soil. The tea plant (Camellia sinensis) has high Al tolerance with abundant monomeric catechins in its leaves, especially epigallocatechin gallate (EGCG), and polymeric proanthocyanidins in its roots (rPA). The role of these polyphenols in the Al resistance of tea plants is unclear. In this study, we observed that these polyphenols could form complexes with Al in vitro, and complexation capacity was positively influenced by high solution pH (pH 5.8), polyphenol type (rPA and EGCG), and high Al concentration. In the 27Al nuclear magnetic resonance (NMR) experiment, rPA-Al and EGCG-Al complex signals could be detected both in vitro and in vivo. The rPA-Al and EGCG-Al complexes were detected in roots and old leaves, respectively, of both greenhouse seedlings and tea garden plants. Furthermore, in seedlings, Al accumulated in roots and old leaves and mostly existed in the apoplast in binding form. These results indicate that the formation of complexes with tea polyphenols in vivo plays a vital role in Al resistance in the tea plant.

Antimicrobial Metabolites Produced by Penicillium mallochii CCH01 Isolated From the Gut of Ectropis oblique, Cultivated in the Presence of a Histone Deacetylase Inhibitor.

Three chemical epigenetic modifiers [5-azacytidine, nicotinamide, and suberoylanilide hydroxamic acid (SAHA)] were applied to induce the metabolites of Penicillium mallochii CCH01, a fungus isolated from the gut of Ectropis oblique. Metabolite profiles of P. mallochii CCH01 were obviously changed by SAHA treatment. Four metabolites (1-4), including two new natural sclerotioramine derivatives, isochromophilone XIV (1) and isochromophilone XV (2), and two known compounds, sclerotioramine (3) and (+)-sclerotiorin (4), were isolated and purified from P. mallochii CCH01 treated with SAHA. Their structures were determined by spectroscopic analyzes. Anti-phytopathogenic activities of the isolated compounds 1-4 were investigated under laboratory conditions, and compound 4 showed broad and important inhibition activities against Curvularia lunata (IC50 = 2.1 µg/mL), Curvularia clavata (IC50 = 21.0 µg/mL), Fusarium oxysporum f. sp. Mornordica (IC50 = 40.4 µg/mL), and Botryosphaeria dothidea (IC50 = 27.8 µg/mL), which were comparable to those of referenced cycloheximide, with IC50 values of 0.3, 5.0, 12.4, and 15.3 µg/mL, respectively. Ingredients 2 and 3 showed selective and potent activities against Colletotrichum graminicola with IC50 values of 29.9 and 9.7 µg/mL, respectively. Furthermore, the antibacterial bioassays showed that compounds 3 and 4 exhibited strong inhibition activities against Bacillus subtilis, with disc diameters of zone of inhibition (ZOI) of 9.1 mm for both compounds, which were a bit weaker than that of referenced gentamycin with a ZOI of 10.8 mm. Additionally, the new metabolite 1 showed a promising activity against Candida albicans (ZOI = 10.5 mm), comparable to that of positive amphotericin B with a ZOI of 23.2 mm. The present results suggest that chemical epigenetic modifier induction was a promising approach to obtaining antimicrobial metabolites encoded by silent biosynthetic genes of P. mallochii.