AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 1
·1-17
·
IF 4
Gu Qifei,Xiao Wuqing,Zhu Yingyin,Zhong Wanling,Sui Xue,Liu Yongchao,Zhang Jie,Wu Huichao,Zhou Rui
Paeoniflorin is a natural pharmaceutical ingredient with a widely biological activity. However, as a hydrophilic drug, the problem of low transdermal rate limits its clinical application. To overcome this shortage, LUVs were used as biocompatible carriers of paeoniflorin in this study. We prepared paeoniflorin-loaded large unilamellar vesicles (LUVs) with W/O/W structure by microfluidics. We used four kinds of chips to prepare paeoniflorin LUVs and explored the effects of the chip structures on LUVs properties applying both experiments and numerical simulations. The difference of fluid mixing mechanisms was analyzed among four different channels, including straight and curved structures. Then we evaluated the differences in skin permeability among the three groups, paeoniflorin aqueous solution group, drug-loaded liposome group and blank liposome & drug mixture group, using the abdominal skin of male mice. The results showed that the structure of the microfluidic channel was a key factor affecting the flow rate and mixing efficiency. The mixing efficiency further affected the liposome size. The mixing efficiency of curved channel was not better than that of a straight channel due to the low flow rate and long mixing time. By the results of transdermal experiments, LUVs could reduce the transdermal time and increase the total transdermal amount. LUVs effectively improved the transdermal absorption efficiency of paeoniflorin. In conclusion, paeoniflorin LUVs with highly efficient transdermal were successfully prepared by using microfluidics. We explored the underlying fluid dynamics that lead to variations in the preparation with different chip structures. The transdermal effect of the LUVs was verified. Graphical
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Nano Research
·
2024
·
IF 9.5
Chen Yue,Zhang Xiaoyu,Jiang Jinzhou,Chen Gaoyu,Zhou Kunhong,Zhang Xinwen,Li Fajing,Yuan Caojin,Bao Jianchun,Xu Xiangxing
All inorganic metal halide perovskite nanocrystals (NCs) have attracted much attention for their outstanding optoelectronic properties, which can be tuned by the composition, surface, size and morphology in nanoscale. Herein, we report the microfluidic synthesis of hollow CsPbBr 3 perovskite NCs through the nanoscale Kirkendall effect. The formation mechanism of the hollow structure (Kirkendall void) controlled by the temperature, flow rate, ratios of precursors and ligands was investigated. Compared with the solid CsPbBr 3 NCs of the same size, the hollow CsPbBr 3 NCs exhibit blue shifts in ultraviolet–visible (UV–vis) absorption and photoluminescence (PL) spectra, and remarkably longer PL average lifetime (~ 98.2 ns). Quantum confinement effect, inner surface induced additional trap states and lattice strain of the hollow CsPbBr 3 NCs were discussed in understanding their unique optoelectronic properties. The hollow CsPbBr 3 NC based photodetector exhibits an outstanding negative photoconductivity (NPC) detectivity of 8.9 × 10 12 Jones. They also show potentials in perovskite NC based photovoltaic and light emitting diodes (LEDs).
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MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 11
·1-11
·
IF 5.3
Huang Yong,Chen Miao,Jiang Fengjuan,Lu Chengzhe,Zhu Qunshan,Yang Yan,Fu Lei,Li Limao,Liu Jia,Wang Zhenguang,Cao Xiaowei,Wei Wei
Studies have found that matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) play an important role in tumorigenesis. In order to detect MMP-9 and IL-6 concentrations with high sensitivity and specificity, an efficient microfluidic-SERS sensing system was prepared based on surface-enhanced Raman scattering (SERS). The aptamer recognition-release mechanism and the dual signal amplification strategy were applied in the sensing system. The sensor system was developed using two kinds of nanomaterials with excellent SERS properties, namely gold-coated iron tetroxide particles (Fe 3 O 4 @AuNPs) and gold nanocages (AuNCs). In addition, Fe 3 O 4 @AuNPs also has magnetic adsorption properties. In the sensing system, single-stranded DNA1 (ssDNA1) and aptamer were modified on Fe 3 O 4 @AuNPs. Single-stranded DNA2 (ssDNA2) and Raman tags were modified on AuNCs. When the target was present, the aptamer bound to the target and detached from the Fe 3 O 4 @AuNPs, and ssDNA2 bound to the exposed ssDNA1. At this time, the Fe 3 O 4 @AuNPs@AuNCs@SERS tag complex was formed, and the SERS signal was enhanced for the first time. Under the action of an external magnet on the microfluidic chip, the complex was magnetized and enriched. The SERS signal was enhanced for the second time. Due to the high affinity between the aptamer and the target object, the sensing system has a strong specificity. The double amplification of the SERS signal gave the system excellent sensitivity. The limit of detection (LOD) relative to MMP-9 and IL-6 were as low as 0.178 pg/mL and 0.165 pg/mL, respectively. The microfluidic-SERS sensing system has a feasible prospect in the early screening of gastric cancer. Graphical
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-17
·
IF 12.6
Zhu Huan,Zhang Zhaoyuan,Jiang Rong,Xu Liangfu,Yang Xiangdi,Chen Jie,Wang Zhenning,Xu Xiao,Liu Zhigang
Radiotherapy (RT) effectiveness is limited by low DNA damage in tumor cells, surrounding tissue harm, and tumor radioresistance with active DNA repair. Herein, we have engineered a two-dimensional nanomaterial consisting of MXene nanosheets at its core, coated with gold nanorods and a cisplatin shell, and further modified with polyvinyl alcohol, referred to as APMP. The APMP exploits its distinctive electronic properties and photothermal effects to augment radiosensitivity and impede DNA damage repair mechanisms. In vitro experiments demonstrate that APMP elevates reactive oxygen species (ROS) production to approximately 2.6 times higher than that achieved with radiotherapy alone, thereby significantly enhancing the sensitivity to radiotherapy. Combining APMP with photothermal therapy (PTT) and RT is a promising glioblastoma treatment strategy, achieving tumor destruction via localized hyperthermia and overcoming radioresistance. This approach achieves precise tumor targeting, reducing side effects and enhancing therapeutic response in preclinical models. The novel core-shell design enables potent radiotherapy-specific radiosensitizers that drive immunogenic cell death, enhancing glioblastoma combination immunotherapy. This universal strategy heralds a new era in integrating radiotherapy sensitizers with immunotherapy. Graphical
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Cell Death & Disease
·
2024
·Vol. 15
·期 7
·1-22
·
IF 8.1
Tan Diaoyi,Miao Daojia,Zhao Chuanyi,Shi Jian,Lv Qingyang,Lu Feiyi,Ruan Hailong,Xiong Zhiyong,Zhang Xiaoping
Aldehyde dehydrogenases superfamily (ALDHs), which are ubiquitously present in various organisms with diverse subcellular localizations, play a crucial role in regulating malignant tumor progression; Nevertheless, their involvement in clear cell renal cell carcinoma (ccRCC) has not been elucidated. In this study, we performed comprehensive bioinformatics analyses on the 19 ALDHs genes, and identified ALDH9A1 as a key contributor in ccRCC. Expression patterns and clinical relevance of ALDH9A1 were determined using bioinformatics analyses, real-time PCR, western blotting, and immunohistochemistry. To explore the underlying mechanism behind the tumor suppressor role of ALDH9A1, RNA sequencing, methylated RNA immunoprecipitation, luciferase reporter assay, mass spectroscopy, immunoprecipitation, mutational studies and immunofluorescence were employed. The impact of ALDH9A1 in ccRCC progression and metabolic programming was assessed through both in vitro and in vivo. Here, this study revealed ALDH9A1 as a tumor suppressor gene in ccRCC. The fat mass and obesity associated protein (FTO) was identified as a demethylase for ALDH9A1 mRNA, resulting in its reduced stability and expression levels in ccRCC. Functional experiments demonstrated that the deficiency of ALDH9A1 in ccRCC promoted tumor proliferation, invasion, migration and lipid accumulation. Mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation. In conclusion, the present study highlights the robust prognostic significance of ALDH9A1 and delivers a comprehensive understanding of ALDH9A1-NPM1-IQGAP2-AKT axis in ccRCC. These findings established a solid research foundation for novel therapeutic strategies for ccRCC patients.
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2012
·Vol. 97
·期 8
·3355-3362
·
IF 3.425
Guo Fei,Xu Haoming,Xu Hongna,Yu Hongwei
Despite directed evolution being a practical and efficient method of improving the properties of enzymes, a trade-off between the targeted property and other essential properties often exists which hinders the efficiency of directed evolution. In our previous work, mutant CVH of an esterase from Rhodobacter sphaeroides with high enantioselectivity was obtained by directed evolution, unfortunately its activity cannot catch another mutant YH. To compensate the trade-off of mutant CVH, site-directed saturation mutagenesis was conducted on four residues, three (Asn62, Met121, and Leu145) were hot spots determined from directed evolution, and one (Tyr27) was introduced to make up the large distance between a mutation (Asn62) and the substrate. A new mutant (HMVY) with high enantioselectivity and comparable activity to YH was obtained. According to the kinetic analysis and molecular dynamics simulations, it was understood that the high enantioselectivity and poor activity of mutant CVH was caused by different decrement of efficiency constants to two isomers, ( R )-, ( S )-methyl mandelate, and the high enantioselectivity and activity of mutant HWVY was caused by improved activity towards the preferred substrate (( S )-methyl mandelate), which provided the interpretation of the trade-off compensation. This work could provide a way to compensate the trade-off of enantioselectivity and activity in the process of enzyme evolution.
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Scientific Reports
·
2017
·
IF 4.259
Kunpeng Li,Rongzhen Zhang,Yan Xu,Zhimeng Wu,Jing Li,Xiaotian Zhou,Jiawei Jiang,Haiyan Liu,Rong Xiao
(S)-carbonyl reductase II (SCRII) from Candida parapsilosis is a short-chain alcohol dehydrogenase/reductase. It catalyses the conversion of 2-hydroxyacetophenone to (S)-1-phenyl-1,2-ethanediol with low efficiency. Sortase was reported as a molecular "stapler" for site-specific protein conjugation to strengthen or add protein functionality. Here, we describe Staphylococcus aureus sortase A-mediated crosslinking of SCRII to produce stable catalysts for efficient biotransformation. Via a native N-terminal glycine and an added GGGGSLPETGG peptide at C-terminus of SCRII, SCRII subunits were conjugated by sortase A to form crosslinked SCRII, mainly dimers and trimers. The crosslinked SCRII showed over 6-fold and 4-fold increases, respectively, in activity and k cat /K m values toward 2-hydroxyacetophenone compared with wild-type SCRII. Moreover, crosslinked SCRII was much more thermostable with its denaturation temperature (T m ) increased to 60 °C. Biotransformation result showed that crosslinked SCRII gave a product optical purity of 100% and a yield of >99.9% within 3 h, a 16-fold decrease in transformation duration with respect to Escherichia coli/pET-SCRII. Sortase A-catalysed ligation also obviously improved T m s and product yields of eight other short-chain alcohol dehydrogenases/reductases. This work demonstrates a generic technology to improve enzyme function and thermostability through sortase A-mediated crosslinking of oxidoreductases.
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INFLAMMATION
·
2012
·Vol. 35
·期 5
·1676-1684
·
IF 1.747
Liu Tengfei,Li Jing,Liu Yuxin,Xiao Nan,Suo Haitao,Xie Kun,Yang Chunliu,Wu Chen
Short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber contribute a significant proportion of daily energy requirement. Furthermore, these compounds are modulators of macrophage function and potential targets for the development of new drugs. The aims of this study were to evaluate the effects of three types of SCFAs (sodium acetate (NaAc), sodium propionate (NaP), and sodium butyrate (NaB)) on the production of NO and inducible nitric oxide synthase (iNOS) and proinflammatory and antiinflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin (IL-1, IL-6, and IL-10)) and to observe the effect of NaAc on inhibiting lipopolysaccharide (LPS)-induced NF-κB activation in LPS-stimulated RAW264.7 cells. The results show that three types of SCFAs (acetate, propionate, and butyrate) reduced the production of proinflammatory factors, including TNF-α, IL-1β, IL-6, and NO, and inhibited the vitality of iNOS. Meanwhile, SCFAs enhanced the production of antiinflammatory cytokine IL-10 in lower concentrations (1–1,200 μmol/L). Like NaB, NaAC inhibited LPS-induced NF-κB activation. These results may hold promise on the role that SCFAs have on the prevention and treatment of various inflammatory conditions.
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JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 2
·1-11
·
IF 2.2
Zhang Xiuping,Wang Shimin,Liang Lixia,Hu Fen,Zhang Xueluo,Cui Xiangrong,Zhang Zhiping,Wu Xueqing
Recurrent spontaneous abortion (RSA) brings tremendous difficulties to clinical treatment and prognosis. Pre-B-cell leukemia homeobox 1 (PBX1), as a functional transcription factor, involves in the regulation of cell apoptosis and proliferation. However, the underlying mechanism of PBX1 in RSA treatment has not been explored. We established a lipopolysaccharide (LPS)-induced abortion model and detected PBX1 expression with real-time PCR, western blot and immunohistochemistry. The PBX1-overexpressed adenovirus (AV-oePBX1) was infected into trophoblast cells treated with LPS to define the function of PBX1 on cell apoptosis, inflammation and NF-κB pathway. A luciferase reporter assay was conducted to validate the transcription regulation of PBX1 on transmembrane and ubiquitin like domain containing 1 (TMUB1). Compared to women with normal abortion, PBX1 was downregulated in the placental villous tissues of RSA patients. The placental tissues of LPS-treated mice also manifested notably reduction of PBX1 at mRNA and protein levels. PBX1 overexpression alleviated inflammation and apoptosis of trophoblast cells. Substantially, PBX1 was negatively correlated with TMUB1, which was highly expressed in RSA patients and LPS-treated mice. Moreover, PBX1 bound to TMUB1 promoter and inhibited its transcription. Interestingly, exogenous TMUB1 abolished the effects of PBX1 on apoptosis, inflammation, and NF-κB signal pathway. In total, PBX1 attenuated cell apoptosis and inflammation, and suppressed NF‐κB signal pathway induced by LPS through downregulating TMUB1 transcription. Therefore, PBX1 may be developed as a novel target for clinical treatment of RSA.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-11
·
IF 14.7
He Lin,Li Menggang,Qiu Longyu,Geng Shuo,Liu Yequn,Tian Fenyang,Luo Mingchuan,Liu Hu,Yu Yongsheng,Yang Weiwei,Guo Shaojun
The precise structural integration of single-atom and high-entropy-alloy features for energy electrocatalysis is highly appealing for energy conversion, yet remains a grand challenge. Herein, we report a class of single-atom Mo-tailored PdPtNiCuZn high-entropy-alloy nanosheets with dilute Pt-Pt ensembles and intrinsic tensile strain (Mo 1 -PdPtNiCuZn) as efficient electrocatalysts for enhancing the methanol oxidation reaction catalysis. The as-made Mo 1 -PdPtNiCuZn delivers an extraordinary mass activity of 24.55 A mg Pt −1 and 11.62 A mg Pd+Pt −1 , along with impressive long-term durability. The planted oxophilic Mo single atoms as promoters modify the electronic structure of isolated Pt sites in the high-entropy-alloy host, suppressing the formation of CO adsorbates and steering the reaction towards the formate pathway. Meanwhile, Mo promoters and tensile strain synergistically optimize the adsorption behaviour of intermediates to achieve a more energetically favourable pathway and minimize the methanol oxidation reaction barrier. This work advances the design of atomically precise catalytic sites by creating a new paradigm of single atom-tailored high-entropy alloys, opening an encouraging pathway to the design of CO-tolerance electrocatalysts.
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Nano Research
·
2024
·
IF 9.5
Lou Yue,Li Jiao,Li Xiaokun,Zhu Zhenyu,Shi Zhan,Xu Biao
Developing acid/base-resistant and low-price microwave-absorbing materials with lighter weight is highly desired for practical applications in extreme environments. Herein, we demonstrate the successful synthesis of the N-doped porous carbon (NC) material with hierarchical pore structure by the spray pyrolysis method. The large specific surface area (S BET = 707.53 m 2 ·g −1 ) of materials enables multiple scattering of incident electromagnetic waves, and N doping greatly enhances the electrical conductivity of the material. Notably, single-atom Zn can adjust the local electronic structure of adjacent sites such as carbon and nitrogen atoms, induce the center of polarization, and thus change the dielectric and electronic properties of the host material. The porous carbon coating of single-atom Zn avoids the deterioration of electromagnetic parameters caused by the accumulation of magnetic particles under high-temperature pyrolysis. At the same time, they can also be used in various complex environments, such as acidic and basic environments. Ultimately, NC-1000, with high surface area, low density, and good chemical stability, obtained a minimum reflection loss (RL min ) of −50.5 dB and an effective absorption bandwidth (EAB) exceeding 5.1 GHz at the thickness of 1.9 mm. After soaking in the strong acid and base solution, the electromagnetic wave absorption performance of the material decreased by < 15%. Widely available raw materials and a simple preparation scheme are expected to expedite industrial mass production for this novel type of materials.
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ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 6
·1-11
·
IF 2.3
Zhuang Cuicui,Zhang Ruoqing,Bai Jiangang,Zhang Xinying,Zhao Jinhui
Escherichia coli ( E. coli ) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli -induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 μmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 μmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1β and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 μmol/L lycopene significantly increased E. coli -induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli -treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli -caused bovine mastitis, providing the new angle of the prevention and management of mastitis.
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