Improved Xylitol Production from d‑Arabitol by Enhancing the Coenzyme Regeneration Efficiency of the Pentose Phosphate Pathway in Gluconobacter oxydans

Gluconobacter oxydans is used to produce xylitol from d-arabitol. This study aims to improve xylitol production by increasing the coenzyme regeneration efficiency of the pentose phosphate pathway in <i>G. oxydans</i>. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were overexpressed in <i>G. oxydans</i>. Real-time PCR and enzyme activity assays revealed that G6PDH/6PGDH activity and coenzyme regeneration efficiency increased in the recombinant <i>G. oxydans</i> strains. Approximately 29.3 g/L xylitol was obtained, with a yield of 73.2%, from 40 g/L d-arabitol in the batch biotransformation with the <i>G. oxydans</i> PZ strain. Moreover, the xylitol productivity (0.62 g/L/h) was 3.26-fold of the wild type strain (0.19 g/L/h). In repetitive batch biotransformation, the <i>G. oxydans</i> PZ cells were used for five cycles without incurring a significant loss in productivity. These results indicate that the recombinant <i>G. oxydans</i> PZ strain is economically feasible for xylitol production in industrial bioconversion

Orbital Orientation-based Theoretical Design of Single-Atom Catalysts for the Hydrogen Evolution Reaction

Hydrogen evolution reaction (HER) is regarded as one of the most effective routes to produce H2, but it usually suffers from the lack of the novel design concept of high-efficiency catalysts, especially in neutral condition. Herein, we report an orbital orientation-based theoretical principle for designing efficient single-atom HER catalysts. Through screening 14 catalysts consisting of the transition-metal single atoms doped into TiO2 (TM1@TiO2) nanosheets, we demonstrate that the d orbital orientation of TM1–Ti1 atomic pairs plays a key role in the regulation of catalytic activities. Among them, Pd1@TiO2 is screened out as an excellent HER catalyst in neutral media, where the Pd-dx2−y2 orbital tends to be exposed due to the existence of Pd1–Ti1 atomic pair and thus promotes OH desorption and the overall hydrogen production. This work provides a new insight through tailoring high-performance orbital catalysts and sheds an orbital-level understanding of the HER mechanism

Tumor-Penetrating Peptide-Functionalized Redox-Responsive Hyperbranched Poly(amido amine) Delivering siRNA for Lung Cancer Therapy

Biosafety and the targeting ability of gene delivery systems are critical aspects for gene therapy of cancer. In this study, we report the synthesis and use of redox-responsive poly­(amido amine) (PAA) with good biocompatibility and biodegradation as a gene carrier material. A tumor-specific tissue penetration peptide, internalizing-RGD (iRGD) was then conjugated to PAA with an amidation reaction. In experiments using H1299 cells, PAA-iRGD was found to have a lower cytotoxicity and higher cellular uptake efficiency compared to PAA. An siRNA, specific to epidermal growth factor receptor (EGFR) that is overexpressed on the lung cancer cell surface and often targeted in lung cancer treatment, was designed to silence EGFR (i.e., siEGFR) for delivery by the gene carrier PAA-iRGD. <i>EGFR</i> gene silencing, apoptosis, antiproliferation, and antitumor effects of PAA-iRGD/siEGFR were evaluated <i>in vitro</i> and <i>in vivo</i>. PAA-iRGD/siEGFR displayed a much higher gene silencing ability compared to PAA and polyethylenimine (25 kDa), significantly inhibited the proliferation and migration of H1299 cells, and elicited significant cell apoptosis. Moreover, intravenously injected PAA-iRGD/siEGFR inhibited lung tumor growth <i>in vivo</i>. These results suggest that PAA-iRGD with good biocompatibility, biodegradation, and targeting ability could be a promising gene delivery system for gene therapy of cancers

Knowledge mapping of therapeutic cancer vaccine from 2013 to 2022: A bibliometric and visual analysis

The investigation of therapeutic cancer vaccines has been ongoing for the past century. Herein, we used VOSviewer and CiteSpace to perform the first global bibliometric analysis of the literature on therapeutic cancer vaccines from 2013 to 2022 aiming to explore the current status and potential research trends. The findings revealed a consistent upward trend in both publication counts and citations. The United States emerged as the leading contributor with the highest number of published papers. Additionally, the analysis of references and keywords indicated that therapeutic cancer vaccines have long been popular topics, whereas neoantigen vaccines, mRNA vaccines, combination strategies, and vaccine delivery systems are emerging research hotspots. This bibliometric study provides a comprehensive and important overview of the current knowledge and potential developments in therapeutic cancer vaccines from 2013 to 2022, which may serve as a valuable reference for scholars interested in further exploring this promising field.</p

Redox-Responsive Biodegradable Polycation Poly(amido amine) Used As Intranasal Vaccine Delivery Systems

Polycations such as polyethylenimine and chitosan have been widely used as mucosal vaccine delivery systems due to their permeation enhancement effect. Preferably, environmentally responding biodegradable polycations would be better carrier materials for mucosal vaccine delivery. Disulfide bond-based redox-sensitive polycations could respond to the higher intracellular glutathione concentration and degrade in the cytoplasm via the breakage of the disulfide bonds, which are particularly suitable for antigen delivery. In this work, we evaluated the potential of redox-sensitive, biodegradable polycation poly­(amido amine) (PAA) as mucosal vaccine carriers. From the primary studies with ovalbumin used as a model protein antigen, it is found that PAA could complex with and encapsulate protein antigen via electrostatic attraction, enhance the cellular uptake of antigen by dendritic cell line DC2.4, prolong antigen residence in nasal cavity, and promote antigen permeation into nasal submucosal layer. Further, Balb/c mice were intranasally immunized with PAA-delivered recombinant hemagglutinin (HA) antigen protein of H7N9 influenza virus. The PAA/HA formulations induced significantly more potent systemic IgG response and mucosal IgA response, higher splenocyte proliferation activity, higher secretion levels of cytokines IFN-γ and IL-4 by splenocytes, more memory CD4⁺ and CD8⁺ T cells, and more DCs expressing MHC II molecule. From the results, the redox-responsive polycation PAA as vaccine carriers helped elicit more potent cellular and humoral immune responses. Particularly, PAA induced much higher cellular immune response compared with previously reported carrier materials. The intelligent PAA could be developed as efficient mucosal vaccine delivery systems for clinical applications

Toxic effects of copper (II) ions on bovine hemoglobin

<p>In this paper, the toxic influence of copper ions (II) on bovine hemoglobin was investigated by the combination of ultraviolet-visible absorption, fluorescence, time-resolved fluorescence, synchronous fluorescence, and circular dichroism spectra. Driven by hydrophobic and electrostatic forces, copper ions (II) could interact with bovine hemoglobin to form bovine hemoglobin-copper ions (II) complex with one binding site. The binding constant (<i>K</i>) was 1.57 × 10⁴, 1.89 × 10⁴ and 2.11 × 10⁴ L/mol at 298, 304, and 310 K, respectively. The binding distance (<i>r</i>) was 4.24 nm. Fluorescence and time-resolved fluorescence spectra showed that bovine hemoglobin quenched by copper ions (II) was a static quenching process. Results of synchronous fluorescence spectra revealed that the microenvironment and the conformation of bovine hemoglobin were changed during the binding reaction. Data of circular dichroism spectra suggested that with the increasing concentration of copper ions (II), the secondary structure of bovine hemoglobin underwent a decrease in <i>α</i>-helix and alteration in backbone microenvironment. Copper ions (II) was thus evidenced to have a certain toxic effect on physical bodies.</p

†Electrorubesopsinae, a new subfamily from Cretaceous Burmese amber, as the possible sister group of Dynamopodinae (Coleoptera: Scarabaeidae)

<p>A new subfamily of Scarabaeidae, †Electrorubesopsinae Bai & Wang subfam. nov., is described from Cretaceous amber of Myanmar (earliest Cenomanian, ∼100 Ma) as the possible sister group of Dynamopodinae. †<i>Electrorubesopsis beuteli</i> Bai & Wang gen. et sp. nov. is the first species of this subfamily, which has probably been long extinct. Its external morphology was analysed and compared with all known genera of Dynamopodinae. A phylogenetic analysis based on 82 morphological characters suggests its placement in a sister relationship between †<i>Electrorubesopsis</i> and <i>Orubesa</i>. The hypothesis of a close relationship between <i>Orubesa</i> (Dynamopodini) and <i>Thinorycter</i> (Thinorycterini) is challenged. †<i>Electrorubesopsis</i> likely lived in a sandy environment or forest.</p> <p><a href="http://zoobank.org/urn:lsid:zoobank.org:pub:15351B5E-337C-49D4-90F0-619269BD1E5A" target="_blank">http://zoobank.org/urn:lsid:zoobank.org:pub:15351B5E-337C-49D4-90F0-619269BD1E5A</a></p

Blood Compatibility Evaluations of Fluorescent Carbon Dots

Because of their unique advantages, fluorescent carbon dots are gaining popularity in various biomedical applications. For these applications, good biosafety is a prerequisite for their use in vivo. Studies have reported the preliminary biocompatibility evaluations of fluorescent carbon dots (mainly cytotoxicity); however, to date, little information is available about their hemocompatibility, which could impede their development from laboratory to bedside. In this work, we evaluated the hemocompatibility of fluorescent carbon dots, which we prepared by hydrothermal carbonization of α-cyclodextrin. The effects of the carbon dots on the structure and function of key blood components were investigated at cellular and molecular levels. In particular, we considered the morphology and lysis of human red blood cells, the structure and conformation of the plasma protein fibrinogen, the complement activation, platelet activation, and in vitro and in vivo blood coagulation. We found that the carbon dots have obvious concentration-dependent effects on the blood components. Overall, concentrations of the fluorescent carbon dots at ≤0.1 mg/mL had few adverse effects on the blood components, but at higher doses, the carbon dots impair the structure and function of the blood components, causing morphological disruptions and lysis of red blood cells, interference in the local microenvironments of fibrinogen, activation of the complement system, and disturbances in the plasma and whole blood coagulation function in vitro. However, the carbon dots tend to activate platelets only at low concentrations. Intravenous administration of the carbon dots at doses up to 50 mg/kg did not impair the blood coagulation function. These results provide valuable information for the clinical application of fluorescent carbon dots

De te fabula narratur: what we can learn from Ukranian cities

<p><b>(a)</b> crown heights <i>δ</i> = 1 μm, 5 μm and 9 μm when axial width <i>b</i> = 1.5 mm. <b>(b)</b> axial widths <i>b</i> = 1.0 mm, 1.5 mm and 2.0 mm when crown height <i>δ</i> = 3 μm.</p

Combined Chemo-photothermal Antitumor Therapy Using Molybdenum Disulfide Modified with Hyperbranched Polyglycidyl

In the treatment of cancers, molybdenum disulfide (MoS₂) has shown great potential as a photoabsorbing agent in photothermal therapy and also as an antitumor drug delivery system in chemotherapy. However, the poor dispersibility and stability of MoS₂ in aqueous solutions limit its applications in cancer therapy. To overcome the shortcomings, MoS₂ was modified mainly by surface adsorption of linear polymers, such as chitosan and poly­(ethylene glycol). As reported, the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts. Herein, we developed hyperbranched polyglycidyl (HPG)-modified MoS₂ (MoS₂–HPG) by absorbing HPG on the MoS₂ surface. The MoS₂–HPG as a novel photoabsorbing agent was also used as a nanoscaled carrier to load antitumor drug doxorubicin hydrochloride (DOX) (MoS₂–HPG–DOX) for combined chemo-photothermal therapy. The physicochemical and photothermal properties of MoS₂–HPG were measured, and the results indicate that MoS₂–HPG had good dispersion and stability in aqueous solutions and also high photothermal conversion efficiency. MoS₂–HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro. Furthermore, the combined chemo-photothermal therapy using MoS₂–HPG–DOX demonstrated better anticancer effect than the individual chemotherapy or photothermal therapy alone. From the results, MoS₂–HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment