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PHARMACEUTICAL RESEARCH · 2023 · IF 3.7

AgNPs-Modified Polylactic Acid Microneedles: Preparation and In Vivo/In Vitro Antimicrobial Studies

Zhang Wenqin,Cai Xiaozhen,Zhang Xinyi,Zou Shiqi,Zhu Danhong,Zhang Qiulong,Chen Jianmin

Objective To prepare polylactic acid microneedles (PLAMNs) with sustained antibacterial effect to avoid skin infection caused by traditional MNs-based biosensors. Methods Silver nanoparticles (AgNPs) were synthesized using an in-situ reduction process with polydopamine (PDA). PLAMNs were fabricated using the hot-melt method. A series of pressure tests and puncture experiments were conducted to confirm the physicochemical properties of PLAMNs. Then AgNPs were modified on the surface of PLAMNs through in-situ reduction of PDA, resulting in the formation of PLAMNs@PDA-AgNPs. The in vitro antibacterial efficacy of PLAMNs@PDA-AgNPs was evaluated using agar diffusion assays and bacterial liquid co-culture approach. Wound healing and simulated long-term application were performed to assess the in vivo antibacterial effectiveness of PLAMNs@PDA-AgNPs. Results The MNs array comprised 169 tiny needle tips in pyramidal rows. Strength and puncture tests confirmed a 100% puncture success rate for PLAMNs on isolated rat skin and tin foil. SEM analysis revealed the integrity of PLAMNs@PDA-AgNPs with the formation of new surface substances. EDS analysis indicated the presence of silver elements on the surface of PLAMNs@PDA-AgNPs, with a content of 14.44%. Transepidermal water loss (TEWL) testing demonstrated the rapid healing of micro-pores created by PLAMNs@PDA-AgNPs, indicating their safety. Both in vitro and in vivo tests confirmed antibacterial efficacy of PLAMNs@PDA-AgNPs. Conclusions In conclusion, the sustained antibacterial activity exhibited by PLAMNs@PDA-AgNPs offers a promising solution for addressing skin infections associated with MN applications, especially when compared to traditional MN-based biosensors. This advancement offers significant potential for the field of MN technology.

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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-10 · IF 16.6

Regulation of species metabolism in synthetic community systems by environmental pH oscillations

Li Shubin,Zhao Yingming,Wu Shuqi,Zhang Xiangxiang,Yang Boyu,Tian Liangfei,Han Xiaojun

Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B ( Saccharomyces cerevisiae ), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO 2 . In addition, a three-species community is constructed with species A′ (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD + and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A′; G6P then enters species C to promote the metabolic reaction that converts NAD + to NADH. The location of species A′ and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA′B, CBA′, and A′CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.

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Nano Research · 2023 · IF 9.9

Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors

Li Shuping,Li Xin,Meng Jiaqi,Bao Weier,Wang Shuang,Ye Peng,Gao Xiao-Dong,Wei Wei

Bacterial outer membrane vesicles (OMVs) are potent immunostimulants of regulating the tumor microenvironment (TME) for immunotherapy, and can be used to deliver drugs. However, the severe systemic inflammatory response triggered by OMVs upon intravenous (i.v.) injection has limited their application. Here, we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin (SA-DOX, AD) onto the surface of OMVs using a matrix metalloproteinase (MMP)-cleavable peptide linker (cL). This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through chemo-immunotherapy. Specifically, the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after i.v. administration, facilitated by the SA decoration on the OMVs surface. Subsequently, the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME, leading to the release of both OMVs and AD. This process provided OMV-induced immunotherapy and DOX-induced chemotherapy, resulting in synergistic tumor inhibition. In conclusion, our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.

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Nature Chemical Biology · 2022 ·Vol. 18 ·期 11 ·1196-1203 · IF 16.174

Structures of the ADGRG2–Gs complex in apo and ligand-bound forms

Lin Hui,Xiao Peng,Bu Rui-Qian,Guo Shengchao,Yang Zhao,Yuan Daopeng,Zhu Zhong-Liang,Zhang Chuan-Xin,He Qing-Tao,Zhang Chao,Ping Yu-Qi,Zhao Ru-Jia,Ma Chuan-Shun,Liu Chang-Hao,Zhang Xiao-Ning,Jiang Dan,Huang Shaohui,Xi Yue-Tong,Zhang Dao-Lai,Xue Chen-Yang,Yang Bai-Sheng,Li Jian-Yuan,Lin Hao-Cheng,Zeng Xu-Hui,Zhao Han,Xu Wen-Ming,Yi Fan,Liu Zhongmin,Sun Jin-Peng,Yu Xiao

Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a G s trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA–ADGRG2–G s provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.

CAS / MDL: 53-16-7
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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 8 ·1-12 · IF 3.3

The Modified Exenatide Microspheres: PLGA-PEG-PLGA Gel and Zinc-Exenatide Complex Synergistically Reduce Burst Release and Shorten Platform Stage

Jiang Wenjing,Gao Xiangjun,Wang Qiuli,Chen Yang,Li Dan,Zhang Xiaoyan,Yang Xinggang

The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 μm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro , behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Graphical Abstract Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo

CAS / MDL: 9002-89-5
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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-9 · IF 16.6

Preferential ice growth on grooved surface for crisscross-aligned graphene aerogel with large negative Poisson’s ratio

Li Meng,Zhao Nifang,Mao Anran,Wang Mengning,Shao Ziyu,Gao Weiwei,Bai Hao

Ice formation on solid surfaces is a ubiquitous process in our daily life, and ice orientation plays a critical role in anti-icing/deicing, organ cryo-preservation, and material fabrication. Although previous studies have shown that surface grooves can regulate the orientation of ice crystals, whether the parallel or perpendicular alignment to the grooves is still under debate. Here, we systematically investigate ice formation and its oriented growth on grooved surfaces through both in situ observation and theoretical simulation, and discover a remarkable size effect of the grooves. With the designability of surface groove patterns, the preferential growth of ice crystals is programmed for the fabrication of a crisscross-aligned graphene aerogel with large negative Poisson’s ratio. In addition, the size effect provides guidance for the design and fabrication of solid surfaces where the effective control of ice orientation is highly desired, such as efficient deicing, long time organ cryo-preservation, and ice-templated materials.

CAS / MDL: 67-68-5 9002-89-5
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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-11 · IF 16.6

Nonredox trivalent nickel catalyzing nucleophilic electrooxidation of organics

Yan Yuandong,Wang Ruyi,Zheng Qian,Zhong Jiaying,Hao Weichang,Yan Shicheng,Zou Zhigang

A thorough comprehension of the mechanism behind organic electrooxidation is crucial for the development of efficient energy conversion technology. Here, we find that trivalent nickel is capable of oxidizing organics through a nucleophilic attack and electron transfer via a nonredox process. This nonredox trivalent nickel exhibits exceptional kinetic efficiency in oxidizing organics that possess the highest occupied molecular orbital energy levels ranging from −7.4 to −6 eV (vs. Vacuum level) and the dual local softness values of nucleophilic atoms in nucleophilic functional groups, such as hydroxyls (methanol, ethanol, benzyl alcohol), carbonyls (formamide, urea, formaldehyde, glucose, and N-acetyl glucosamine), and aminos (benzylamine), ranging from −0.65 to −0.15. The rapid electrooxidation kinetics can be attributed to the isoenergetic channels created by the nucleophilic attack and the nonredox electron transfer via the unoccupied e g orbitals of trivalent nickel (t 2g 6 e g 1 ). Our findings are valuable in identifying kinetically fast organic electrooxidation on nonredox catalysts for efficient energy conversions.

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JOURNAL OF MATERIALS SCIENCE · 2023 ·Vol. 58 ·期 46 ·17483-17499 · IF 4.5

Flower-like MoS2/cotton fiber-derived TiO2 composites with strong electromagnetic wave absorption performance

Tang Qin,Chen Hui,Shen Jun

The flower-like MoS 2 /cotton fiber-derived TiO 2 (MoS 2 /CF–TiO 2 ) composites were successfully prepared through the bio-template method and hydrothermal reaction. The influence of TiO 2 morphology and content on the electromagnetic wave (EMW) absorption performance of the composites was explored. The enhancement effect and mechanism of the heterostructure formed by MoS 2 and CF–TiO 2 on the EMW absorption performance were analyzed. The results showed that when CF–TiO 2 was added with a titanium-molybdenum atomic ratio of 2:1, the MoS 2 /CF–TiO 2 composites reached the minimum reflection loss (RL) of − 42.4 dB at 6.4 GHz when the thickness was 4.0 mm. The strong EMW absorption performance of MoS 2 /CF–TiO 2 composites could be attributed to the improvement of impedance matching. The good interface contact between the tubular CF–TiO 2 and flower-like MoS 2 not only increased the specific surface area of the material, but also greatly improved the conductivity of the material, enhancing the conduction loss and various polarization losses.

CAS / MDL: 5593-70-4 9022-96-2
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JOURNAL OF NANOPARTICLE RESEARCH · 2023 ·Vol. 25 ·期 11 ·1-13 · IF 2.5

Impact of immunomagnetic nanoparticle size on capture efficiency, bioactivity, and proliferation ability of circulating tumor cells

Zhang Jiabao,Jian Xiaojuan,Bai Shunfeng,Xu Guoli,Du Meiling,Guo Chen,Guan Yueping

The application of immunomagnetic nanoparticles (IMNs) enables the isolation of rare circulating tumor cells (CTCs) from blood. Precise capture of CTCs with specific tumor phenotypes is achieved by attaching specific ligands to the surface of IMNs. The captured CTCs need to exhibit high bioactivity and proliferation ability for subsequent detection after co-culturing. The process of CTC enrichment using magnetic nanoparticles entails several issues, such as nonspecific capture and biological toxicity. Modifying the size of nanoparticles allows for altering the capture efficiency of nanoparticles for CTCs, as well as their biological activity and proliferation ability. In this study, two different sizes of magnetic nanoparticles are utilized to capture CTCs under diverse conditions. The capture efficiency of magnetic nanoparticles is assessed at different incubation times, along with determining the time needed to achieve and sustain the optimal capture efficiency. Fluorescence staining is employed to detect the bioactivity and cellular integrity of the captured CTCs. Subsequent to co-culturing with nanoparticles, the number of CTCs is measured every 24 h, and the survival rate is determined after 96 h. Graphical abstract

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Chinese Medicine · 2023 ·Vol. 18 ·期 1 ·1-14 · IF 4.9

Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy

Guo Zhaopei,Wong Ka Hong,Li Enze,Zhou Xingzhi,Jiang Di,Gao Jiebing,Chen Meiwan

Background The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.MethodA polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).Results The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.Conclusion This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.Graphical Abstract

CAS / MDL: 67-68-5
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Journal of Rubber Research · 2023 ·Vol. 26 ·期 5 ·391-405 · IF 1.3

Preparation and ablation properties study of a single component ceramifiable RTV silicone rubber

Wang Xuebao,Huang Ao,Zhao Min,Li Jianhua,Li Sicheng,Li Xiaobin

Room temperature vulcanised (RTV) silicone rubber is widely used in daily life. Ordinary and traditional flame-retarding RTV silicone rubber are easy to turn into brittle char layer or ashes without any self-supporting and bonding ability after experiencing a combustion process, which could not inhibit the secondary disasters after fire. To improve the fire-resistance performances of RTV silicone rubber, a new single component ceramifiable RTV silicone rubber was prepared in this work. The tack-free time, mechanical properties and thermal properties of different formulations were tested. The flexural strength and adhesion strength of the ceramic residues were studied by orthogonal designed experiments, which exhibited the maximum of 8.80 and 0.300 MPa after sintering at 1000 °C, respectively. The ceramifying process of the single component ceramifiable RTV silicone rubber at high temperatures was also investigated. These results will provide a basis for the development of fire-resistant silicone adhesive with better performance that can meet the actual needs.

CAS / MDL: 77-58-7
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MICROCHIMICA ACTA · 2023 ·Vol. 190 ·期 10 ·1-10 · IF 5.7

Traceable value of immunoglobulin G against receptor-binding domain of SARS-CoV-2 confirmation and application to point-of-care testing system development

Liang Zhanwei,Lu Xin,Jiao Xueshima,He Yi,Meng Bo,Xie Jie,Qu Ziyu,Zhu Manman,Gong Xiaoyun,Zhao Yang,Peng Tao,Fang Xiang,Dai Xinhua

A highly purified and bioactive immunoglobulin G monoclonal antibody against receptor-binding domain of SARS-CoV-2 (RBD-IgG-MAb) has been accurately quantified by amino acid determination using isotope dilution liquid chromatography–mass spectrometry. Absolute quantification of RBD-IgG-MAb was achieved by averaging 4 amino acid certified reference materials, which allows the quantitative value (66.1 ± 5.8 μg/L) to be traced to SI unit (mol). Afterwards, the RBD-IgG-MAb was employed as control and calibration compound for the development of a point-of-care testing (POCT) system based on colloidal gold lateral flow immunoassay, which aimed to rapidly and accurately detect the level of protective RBD-IgG after vaccination. Under the detection parameters, a sigmoidal curve has been plotted between signal intensity and the logarithmic concentration for quantitative detection with the limit of detection of about 0.39 μg/mL. The relative standard deviations of intra-assay and inter-assay were lower than 2.3% and 14%, and the recoveries ranged from 87 to 100%, respectively. Fingertip blood samples from 37 volunteers after vaccination were analyzed by the POCT system; results showed that levels of RBD-IgG in 33 out of 37 samples ranged from 0.45 to 2.46 μg/mL with the average level of 0.91 μg/mL. The developed POCT system has been successfully established with the quantity-traceability RBD-IgG-MAb as control and calibration compound, and the scientific contribution of this work can be promoted to other areas. Graphical Abstract

CAS / MDL: 9005-64-5 25322-68-3
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