ABSTRACT
Type I interferon (IFN-I) is a potent immune modulator intricately involved in regulating tumor immunity. Meanwhile, the integrity of the IFN-I signaling pathway is essential for radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the clinical application of IFN-I remains challenging due to its non-specific cytotoxicity and limited half-life. To overcome these limitations, we developed a gene delivery platform, CRISPR-V, enabling the rapid creation of novel HSV-1 oncolytic viruses. Utilizing this platform, we created an oncolytic virus, OVH-IFNß, in which the IFNß gene was incorporated into the HSV-1 genome. However, exogenous IFNß expression significantly inhibited OVH-IFNß replication. Through transcriptome data analyses, we identified several ISG genes inhibiting OVH-IFNß replication. By gene knockout and functional studies of the downstream effectors, we confirmed the prominent antiviral activities of protein kinase R (PKR). To balance the antitumor and antiviral immunity of IFNß, we developed a novel HSV-1 oncolytic virus, OVH-IFNß-iPKR, which can express IFNß while inhibiting PKR, leading to a potent antitumor immunity while reducing the antiviral capacity of IFNß. OVH-IFNß-iPKR shows a strong ability to induce immunogenic cell death and activate tumor-specific CD8+ T cells, leading to de novo immune responses and providing a novel strategy for tumor immunotherapy.
Subject(s)
Herpesvirus 1, Human , Interferon-beta , Oncolytic Viruses , eIF-2 Kinase , Animals , Humans , Mice , Cell Line, Tumor , eIF-2 Kinase/metabolism , eIF-2 Kinase/genetics , Herpesvirus 1, Human/genetics , Interferon-beta/genetics , Interferon-beta/metabolism , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/genetics , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Virus ReplicationABSTRACT
Type I interferons (IFN-I) play pivotal roles in tumor therapy for three decades, underscoring the critical importance of maintaining the integrity of the IFN-1 signaling pathway in radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the specific mechanism by which IFN-I contributes to these therapies, particularly in terms of activating dendritic cells (DCs), remains unclear. Based on recent studies, aberrant DNA in the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway, which in turn produces IFN-I, which is essential for antiviral and anticancer immunity. Notably, STING can also enhance anticancer immunity by promoting autophagy, inflammation, and glycolysis in an IFN-I-independent manner. These research advancements contribute to our comprehension of the distinctions between IFN-I drugs and STING agonists in the context of oncology therapy and shed light on the challenges involved in developing STING agonist drugs. Thus, we aimed to summarize the novel mechanisms underlying cGAS-STING-IFN-I signal activation in DC-mediated antigen presentation and its role in the cancer immune cycle in this review.
Subject(s)
Interferon Type I , Neoplasms , Humans , Nucleotidyltransferases/metabolism , Signal Transduction , Interferon Type I/metabolism , Neoplasms/metabolism , Dendritic Cells/metabolism , Immunity, InnateABSTRACT
We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, high-cordycepin-producing strain C. militaris GYS60, and low-cordycepin-producing strain C. militaris GYS80. Differentially expressed genes were identified from the transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. Gene Ontology analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By Clusters of Orthologous Groups of Proteins and Kyoto Encyclopedia of Genes and Genomes analyses, eight genes were significantly upregulated: five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3',5'-cyclic AMP production. Cyclic AMP accelerated 3'-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Adenosine addition increased cordycepin production by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.
ABSTRACT
Salidroside has been widely used in anti-tumor, cardiovascular, and cerebrovascular protection. However, there are few reports of its use for wound repair. Herein, salidroside inflammation-targeted emulsion gel and non-targeted emulsion gel were developed for wound repair. The inflammation-targeted emulsion gels showed an overall trend of better transdermal penetration and lower potential than non-targeted emulsion gels (-58.7 mV and -1.6 mV, respectively). The apparent improvement of the trauma surface was significant in each administration group. There was a significant difference in the rate of wound healing of the rats between each administration group and the model group at days 7 and 14. Pathological tissue sections showed that inflammatory cells in the epidermis, dermis, and basal layer were significantly reduced, and the granulation tissue was proliferated in the inflammation-targeted emulsion gel group and the non-targeted emulsion gel group. Regarding the expressions of EGF and bFGF, the expressions of bFGF and EGF in the tissues of the inflammation-targeted group at days 7, 14, or 21 were significantly higher than that of the non-targeted emulsion gel group and the model group, both of which were statistically significant compared with the model group (p < 0.05). These results demonstrated that salidroside has the potential as an alternative drug for wound repair.
Subject(s)
Epidermal Growth Factor , Wound Healing , Rats , Animals , Emulsions , Inflammation/drug therapy , GelsABSTRACT
Cobalt coordinated covalent organic frameworks have attracted increasing interest in the field of CO2 photoreduction to CO, owing to their high electron affinity and predesigned structures. However, achieving high conversion efficiency is challenging since most Co related coordination environments facilitate fast recombination of photogenerated electron-hole pairs. Here, we design two kinds of Co-COF catalysts with oxygen coordinated Co atoms and find that after tuning of coordination environment, the reported Co framework catalyst with Co-O4 sites exhibits a high CO production rate of 18000 µmol g-1 h-1 with selectivity as high as 95.7% under visible light irradiation. From in/ex-situ spectral characterizations and theoretical calculations, it is revealed that the predesigned Co-O4 sites significantly facilitate the carrier migration in framework matrixes and inhibit the recombination of photogenerated electron-hole pairs in the photocatalytic process. This work opens a way for the design of high-performance catalysts for CO2 photoreduction.
ABSTRACT
The emission of NH3 into atmosphere is seriously harmful for human health and public safety, thus the capture and recovery of NH3 from ammonia emissions is highly desirable. In recent years, many kinds of solid adsorbents have been exploited to absorb NH3. However, these materials do not show the advantages of high uptake capacity and good recyclability at the same time. Here, nontoxic and low cost few-layer BiI3 nanosheets have been prepared from bulk BiI3 powder by a simple and efficient liquid phase exfoliation strategy using green solvents and then applied for the NH3 capture for the first time. The results show that the adsorption capacity of NH3 of BiI3 nanosheets reaches up to 22.6 mmol/g at 1.0 bar and 25 °C, which approaches the record value for NH3 adsorption. Importantly, the NH3 uptake in BiI3 nanosheets is completely reversible and no clear loss in uptake capacity is observed after 10 cycles of adsorption-desorption. Furthermore, the BiI3 nanosheets exhibit remarkable selectivity for the separation of NH3/CO2 at 70 °C with theoretical selectivity coefficient of 700, which is promising for the selective separation of NH3 and CO2 in hot tail gas of some industrial processes. Mechanism studies indicate that such superior NH3 capacity, excellent reversibility and remarkable selectivity are primarily attributed to the Bi3+-NH3 coordination interactions.
ABSTRACT
In recent years, metal-organic frameworks (MOFs) have been explored as emulsifiers for the fabrication of Pickering emulsions and then used for hybrid material synthesis and interface catalysis. Nevertheless, stimuli-responsive Pickering emulsions stabilized by MOFs have been rarely reported so far, although they are of great importance for fundamental research studies and practical applications. Herein, for the first time, triethylenetetramine (TETA)-functionalized MOFs (ZIF-90/TETA) have been designed, synthesized, and used for fabricating CO2-/N2-response Pickering emulsions. It is shown that even at the ZIF-90/TETA content of 0.25 wt %, the functional MOF can still efficiently emulsify n-hexane and water to form a high internal phase Pickering emulsion. Importantly, the Pickering emulsion can be easily and reversibly switched between emulsification and demulsification by bubbling of CO2 and N2 alternatively at atmospheric pressure. The possible mechanism of the CO2/N2 switchable emulsion is investigated by zeta potential, water contact angle, interfacial tension, 13C NMR spectroscopy, and an optical microscope. It is found that the acid-base reaction of CO2 with TETA anchored on the surface of ZIF-90 leads to the production of hydrophilic ammonium bicarbonate and carbamate, which results in the emulsification of the Pickering emulsion. However, when N2 is bubbled to remove CO2, the reverse reaction takes place to cause the demulsification of the Pickering emulsion. Moreover, the CO2/N2 switchable Pickering emulsion has been successfully used as a microreactor for Knoevenagel reactions to demonstrate a highly efficient integration of chemical reaction, product separation, and ZIF-90/TETA recycling for a sustainable chemical process.
ABSTRACT
A multifunctional plasma mutation system (MPMS) method was used to create high cordycepin-yielding mutations from wild Cordyceps militaris, which yielded many viable mutants, many of which produced more cordycepin compared to the wild strain. One particular mutant strain (GYS60) produced 7.883 mg/mL, which is much higher than those reported to date and is more than 20 times higher than that of the wild strain, whereas the cordycepin production of another viable mutant (GYS80) was almost zero. The extraction and purification of cordycepin, using the fermentation broth of C. militaris GYS60, was also investigated. Cordycepin was extracted by using AB-8 macroporous resin and purified by using reversed-phase column chromatography. When the sample was adsorbed onto the macroporous resin, 20% ethanol was used as the desorption solvent yielding various fractions. The fractions containing cordycepin were loaded onto a reversed-phase chromatography column packed with octadecyl bonded silica as the stationary phase and ethanol (95%)/acetic acid solution (5%) at pH 6.0 as the mobile phase. The combination of this two-step extraction-purification process yielded cordycepin at 95% purity with a total recovery rate of 90%.
Subject(s)
Cordyceps/genetics , Cordyceps/metabolism , Deoxyadenosines/biosynthesis , Plant Extracts/biosynthesis , Agaricales/genetics , Agaricales/metabolism , Chromatography, High Pressure Liquid , Cordyceps/chemistry , Cordyceps/growth & development , Culture Media/metabolism , Deoxyadenosines/analysis , Deoxyadenosines/isolation & purification , Fermentation , Mutagenesis , Mutation , Plant Extracts/analysis , Plant Extracts/isolation & purificationABSTRACT
A two-dimensional (2D) nanoporous Ni(OH)2 film was successfully developed from triethanolamine (TEA) as the alkali source and soft template using a scalable hydrothermal technique. The nanostructured Ni(OH)2 film was flexible and translucent, and could be directly compressed on a current collector. Owing to the uniform well-defined morphology and stable structure, the Ni(OH)2 film binder-free electrode displayed a high specific capacity, exceptional rate capability, and admirable cycle life. The specific capacitance was 453.6 mA h g-1 (1633 F g-1) at 0.5 A g-1. The assembled Ni(OH)2//activated carbon (AC) asymmetric supercapacitor (ASC) device had an energy density of 58.7 W h kg-1 at a power density of 400 W kg-1. These prominent electrochemical properties of Ni(OH)2 were attributed to the high electrical conductivity, high surface area, and unique porous architecture. Free tailoring, binder-free, and direct pressing were the most significant achievements of the Ni(OH)2 film in the development of high-performance energy storage devices.
ABSTRACT
The nanoplasmonic metal-driven photocatalytic activity depends heavily on the spacing between metal nanoparticles (NPs) and semiconductors, and this work shows that ethylene glycol (EG) is an ideal candidate for interface spacer. Controlling the synthetic systems at pH 3, the composite of Ag NPs with EG-stabilized amorphous TiO2 (Ag/TiO2-3) was synthesized by the facile light-induced reduction. It is verified that EG spacers can set up suitable geometric arrangement in the composite: the twin hydroxyls act as stabilizers to bind Ag NPs and TiO2 together and the nonconductive alkyl chains consisting only of two CH2 are able to separate the two building blocks completely and also provide the shortest channels for an efficient transfer of radiation energies to reach TiO2. Employed as photocatalysts in hydrogen evolution under visible light, amorphous TiO2 hardly exhibits the catalytic activity due to high defect density, whereas Ag/TiO2-3 represents a remarkably high catalytic efficiency. The enhancement mechanism of the reaction rate is proposed by the analysis of the compositional, structural, and optical properties from a series of Ag/TiO2 composites.
ABSTRACT
The charge transfer and active sites of metal-free imidazolium-based composites were unveiled by an electrochemical method with high sensitivity and selectivity due to the specific donor-acceptor coupling of imidazolium with NO2-.
ABSTRACT
Rhodamine B (RhB) has often been used as a model pollutant, but its photocatalytic mechanism is still controversial. Herein, Ag NPs were sandwiched between CdS QDs and amorphous-TiO2 (a-TiO2) with the intent to build a CdS/Ag/a-TiO2 catalyst with highly selective oxidation activity. When rhodamine B (RhB) was used as the model organic compound, the CdS/Ag/a-TiO2 composite can not only modulate radical generation but also improve the conversion ratio of RhB to rhodamine 110 (Rh-110) to as high as 82% at 80 min during the visible-light irradiation. A series of the radical scavenging experiments revealed that CdS/Ag/a-TiO2 composites could modulate the effects of hydroxyl radicals (·OH) and superoxide anion radicals (·O2 -) at different reaction stages so that the overoxidation of RhB and Rh-110 were repressed. Therefore, the transient state protection mechanism of selective oxidation of RhB was proposed to explain the reaction selectivity for Rh-110. Although the effects of both ·O2 - and ·OH are important during the photocatalytic selective oxidation of RhB, it is shown that the selective oxidation of RhB would be performed when the effect of ·O2 - is bigger than the ·OH, if not, RhB would be oxidized unselectively. Meanwhile, this may provide a new strategy for modulating radical generation in the photocatalysis of water phases.
ABSTRACT
This study proposes a facile solvothermal synthesis of nickel tungstate (NiWO4) nanowires for application as a novel cathode material for supercapacitors. The structure, morphology, surface area and pore distribution were characterized and their capacitive performances were investigated. The results showed that the NiWO4 nanowires synthesized in ethylene glycol solvent could offer a high specific capacitance of 1190 F g-1 at a current density of 0.5 A g-1 and a capacitance retaining ratio of 61.5% within 0.5-10 A g-1. When used as a cathodic electrode of an asymmetric supercapacitor (ASC), the NiWO4 nanowire based device can be cycled reversibly in a high-voltage region of 0-1.7 V with a high specific capacitance of 160 F g-1 at 0.5 A g-1, which therefore contributed to an energy density of 64.2 W h kg-1 at a power density of 425 W kg-1. Moreover, 92.8% of its initial specific capacitance can be maintained after 5000 consecutive cycles (5 A g-1). These excellent capacitive properties make NiWO4 a credible electrode material for high-performance supercapacitors.
ABSTRACT
This work developed a facile colloidal route to synthesize BH4--capped PdxAgy nanoparticles (NPs) in water using the reducing ionic liquids of [Cnmim]BH4, and the resulting NPs were prone to form the nanocomposites with [amim]+-modified reduced graphene (RG). The removal of the metal-free inorganic ions of BH4- can create the profoundly exposed interfaces on the PdxAgy NPs during the electrooxidation, and favor the ethanol oxidation reaction (EOR) in lowering energy barrier. The counterions of [Cnmim]+ can gather ethanol, OH- ions, and the reaction intermediates on catalysts, and synergistically interact with RG to facilitate the charge transfer in nanocomposites. The interface-modified RG nanosheets can effectively segregate the PdxAgy NPs from aggregation during the EOR. Along with the small size of 4.7 nm, the high alloying degree of 60.2%, the large electrochemical active surface area of 64.1 m2 g-1, and the great peak current density of 1501 mA cm-2 mg-1, Pd1Ag2@[C2mim]BH4-amimRG nanocomposite exhibits the low oxidation potentials, strong poison resistance, and stable catalytic activity for EOR in alkaline media, and hence can be employed as a promising anodic catalyst in ethanol fuel cells.
ABSTRACT
The development of a simple, template-free, and one-step strategy to synthesize nanostructured Au architectures with fascinating morphology is highly desirable and technically important due to their valuable applications in varied fields. In this work, the "green" strategy of "tunable ionic liquids-water (ILs-H2O) interfacial synthesis" developed previously by us is utilized for feasible synthesis of gold needle mushroom-like micro/nanostructures at the 1,3-dibutylimidazolium bis(trifluoromethylsulfonyl)imide ([C4bim][Tf2N]) - water interface and ambient conditions. The as-obtained gold needle mushrooms (AuNMs) have been characterized and analyzed systemically by scanning electron microscopy, X-ray powder diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. It is shown that the as-prepared AuNMs can be used as substrates to perform surface enhanced Raman scattering (SERS) investigation with striking SERS sensitivity. By employing ILs with different alkyl chain lengths of the imidazolium cations and/or different nature of anions, Au nanomaterials with diverse morphologies can be easily prepared at different ILs-H2O interfaces. Based on the analysis of the control experiments, the growth and formation of AuNMs at the [C4bim][Tf2N]-H2O interface have been discussed.
ABSTRACT
Streptococcal protein G (SPG), which is an antigen of the Streptococcus sp. cell wall, is important due to its high specificity to immunoglobulin (Ig), as compared with staphylococcal protein A. However, the cost of commercial recombinant (r)SPG has so far hindered further research into the application of rSPG. Efficient high cell density fermentation of genetically modified Escherichia coli and purification technology have previously been studied as a means to obtain rSPG. In the present study, the immunological characterization of purified rSPG was compared with commercial SPG via western blot analysis. The results of the present study demonstrated that the IgGbinding capacity of purified rSPG was markedly higher, as compared with commercial SPG. Furthermore, purified rSPG crosslinked with Q Sepharose® Fast Flow exhibited excellent affinity with IgG in murine serum. In order to obtain relatively pure and accurate rSPG, the purified rSPG was identified by Nanoflow Liquid ChromatographyMass Spectrometry (MS)/MS spectrum. The results indicated that the two peptide fragments of purified rSPG corresponded to the Streptococcus sp. GX7805 protein G as listed in the National Center for Biotechnology Information database. The method described in the present study offers a novel practical method for the verification of rSPG in relatively pure form, in order to purify IgG or carry out immunolabeling processes.
Subject(s)
Bacterial Proteins/isolation & purification , Gene Expression Regulation, Bacterial , Streptococcus/genetics , Bacterial Proteins/genetics , Escherichia coli/genetics , Immunoglobulin G/metabolism , Protein Binding , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Staphylococcal Protein A , Streptococcus/metabolism , Tandem Mass SpectrometryABSTRACT
Recombinant Streptococcus Protein G (PG) is a cell wall protein, which, when combined with mammal immunoglobulin, is used in separating antibody technology. High-density fermentation technologies using an engineered recombinant PG-producing bacteria as well as PG separation and purification technologies have a direct impact on the availability and application of PG. Through primary and secondary seed cultivation, a recombinant E. coli strain was subjected to high-density fermentation with controlled feed supplement concentration under stimulation with isopropyl ß-D-1-thiogalactopyranoside. The present study investigated the effect of factors including inoculum size, oxygen levels, pH and the cultivating method on the fermentation process, as well as the effect of the separation and purification technologies, including ultrasonication, nickel column affinity chromatography, Sephadex G-25 gel filtration chromatography and diethylaminoethanol-sepharose fast flow ion exchange chromatography on the yield and purity of PG. The efficiency of extraction was detected using SDS-PAGE. High-density fermentation yielded 80-150 g/l of bacteria and 1 g PG was obtained from one liter broth. The present study delivered a highly efficient novel method via which PG can be obtained at a high concentration and a purity >95%.
Subject(s)
Bacterial Proteins/biosynthesis , Escherichia coli/genetics , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Chromatography, Affinity , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Escherichia coli/drug effects , Escherichia coli/metabolism , Fermentation , Gene Expression , Genetic Engineering , Hydrogen-Ion Concentration , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Sonication , Thiogalactosides/pharmacologyABSTRACT
Thiol-functionalized dialkylimidazolium bromide was synthesized, and used as a stabilizer to prepare monodisperse silver nanocrystals through a facile one-pot aqueous approach. It is shown that the multipurpose ligands play a vital role in improving the performance of nanocrystals. The mechanisms of dialkylimidazolium-mediated promotion were analyzed on the basis of the physicochemical properties of the specifically designed ligand.
Subject(s)
Imidazoles/chemistry , Mercury/analysis , Nanoparticles/chemistry , Silver/chemistry , Catalysis , Excipients/chemical synthesis , Excipients/chemistry , Imidazoles/chemical synthesis , Mercury/chemistry , Microscopy, Electron, TransmissionABSTRACT
The novel thiol-functionalized ionic liquids (ILs), 1-(10-mercaptodecyl)-3-methylimidazolium chloride ([HS-C10mim]Cl) and 1-(4-mercaptobutyl)-3-methylimidazolium chloride ([HS-C4mim]Cl), were synthesized by introducing thiol groups onto the alkyl chains in imidazolium-based ILs. The ILs exhibit strong affinity toward CdSe/CdS quantum dots (QDs), and can readily transfer the QDs from organic phases to aqueous phase. The IL-capped CdSe/CdS QDs are extremely soluble in water, and their photochemical stability was measured by absorption spectra. It is shown that the [HS-C10mim]Cl-capped QDs in water present much better anti-photooxidation than [HS-C4mim]Cl-capped those. The measurements of Zeta potential and hydrodynamic diameter reveal that the enhanced mechanism of [HS-C10mim]Cl depends mainly on the specific physico-chemical properties of the ILs. In particular, CdSe/CdS QDs with high surface potential, small hydrodynamic diameter, and optimal photochemical stability can be harvested by the solubilization of free [HS-C10mim]Cl in ligand shells of the QDs.
ABSTRACT
In this paper, microbial transformation of norkurarinone (1) by Cunninghamella blakesleana AS 3.970 was investigated and seven transformed products were isolated and characterized as kurarinone (2), 4â³,5â³-dihydroxykurarinone (3), 6â³-hydroxyl-2'-methoxyl-norkurarinone 7-O-ß-d-glucoside (4), 6â³-hydroxyl-norkurarinone 4'-O-ß-d-glucoside (5), 4â³,5â³-dihydroxynorkurarinone (6), 7-methoxyl-norkurarinone (7), and 7-methoxyl-4â³,5â³-dihydroxynorkurarinone (8), respectively. Among them, 3-5 are new compounds, and the glycosylation reaction in microbial transformation process was reported rarely. In addition, the cytotoxicities of transformed products (1-8) were also investigated.