المؤلفون: Li Wang, Qunyan Yao, Xuerui Guo, Bingmei Wang, Jingyi Si, Xingye Wang, Shisong Jing, Ming Yan, Yan Shi, Guangqi Song, Xizhong Shen, Jiyu Guan, Yicheng Zhao, Changfeng Zhu

المصدر: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: Tetrahedral framework nucleic acid, Small activating RNA, Pancreatic ductal adenocarcinoma, CCAAT/enhancer-binding protein alpha, Aptamer, RNA delivery, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5

الوصف: Abstract Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1477-3155Test

الوصول الحر: https://doaj.org/article/29823b50b96a453db79b7b3416bb8c4eTest

المؤلفون: Junsheng Luo, Bowen Liu, Haomiao Yin, Xin Zhou, Mingjian Wu, Hongyang Shi, Jiyun Zhang, Jack Elia, Kaicheng Zhang, Jianchang Wu, Zhiqiang Xie, Chao Liu, Junyu Yuan, Zhongquan Wan, Thomas Heumueller, Larry Lüer, Erdmann Spiecker, Ning Li, Chunyang Jia, Christoph J. Brabec, Yicheng Zhao

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract The development of a robust quasi-ohmic contact with minimal resistance, good stability and cost-effectiveness is crucial for perovskite solar cells. We introduce a generic approach featuring a Lewis-acid layer sandwiched between dopant-free semicrystalline polymer and metal electrode in perovskite solar cells, resulting in an ideal quasi-ohmic contact even at elevated temperature up to 85 °C. The solubility of Lewis acid in alcohol facilitates nondestructive solution processing on top of polymer, which boosts hole injection from polymer into metal by two orders of magnitude. By integrating the polymer-acid-metal structure into solar cells, devices exhibit remarkable resilience, retaining 96% ± 3%, 96% ± 2% and 75% ± 7% of their initial efficiencies after continuous operation in nitrogen at 35 °C for 2212 h, 55 °C for 1650 h and 85 °C for 937 h, respectively. Leveraging the Arrhenius relation, we project an impressive T 80 lifetime of 26,126 h at 30 °C.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/e6f7878e61994854beb08b119045c944Test

المؤلفون: Xuerui Guo, Li Wang, Jinlong Zhang, Quan Liu, Bingmei Wang, Da Liu, Fei Gao, Gongga Lanzi, Yicheng Zhao, Yan Shi

المصدر: npj Biofilms and Microbiomes, Vol 10, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: Microbial ecology, QR100-130

الوصف: Abstract Limitations in the clinical treatment of Staphylococcus aureus (S. aureus) infections have arisen due to the advent of antibiotic-resistant strains. Given the immense potential of therapeutic strategies targeting bacterial virulence, the role of MgrA as a pivotal virulence determinant in S. aureus-orchestrating resistance, adherence, and hundreds of virulence targets—becomes indispensable. In this investigation, leveraging advanced virtual screening and fluorescence anisotropy assays, we discerned methylophiopogonanone A (Mo-A), a flavonoid derivative, as a potent disruptor of the MgrA-DNA interaction nexus. Subsequent analysis revealed that Mo-A effectively inhibits the expression of virulence factors such as Hla and Pvl in S. aureus and markedly reduces its adhesion capability to fibrinogen. On a cellular landscape, Mo-A exerts a mitigating influence on the deleterious effects inflicted by S. aureus USA300 on A549 cells. Furthermore, our data indicate that Mo-A downregulates the transcription of genes associated with immune evasion, such as nucleases (nuc), Staphylococcal Chemotaxis Inhibitory Protein (chips), and Staphylococcal Complement Inhibitor (scin), thereby undermining immune escape and amplifying neutrophil chemotaxis. Upon application in an in vivo setting, Mo-A assumes a protective persona in a murine model of S. aureus USA300-induced pneumonia and demonstrates efficacy in the Galleria mellonella infection model. Of note, S. aureus displayed no swift acquisition of resistance to Mo-A, and the effect was synergistically enhanced when used in combination with vancomycin. Our findings add substantive weight to the expanding field of virulence-targeted therapeutic strategies and set the stage for more comprehensive exploration of Mo-A potential in combating antibiotic-resistant S. aureus.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2055-5008Test

الوصول الحر: https://doaj.org/article/c64ee4fd07ce4bf9a3894eaa50f07119Test

المؤلفون: Yuanyuan Liu, Xuan Liu, Siyue Wei, Zhaoyu Cheng, Yidan Xian, Yicheng Zhao, Jun Ma, Jiageng Chen, Zhongdan Chen, Jie Yang, Fengli Liu, Maohe Yu, Zhuang Cui, Changping Li

المصدر: Journal of Virus Eradication, Vol 10, Iss 2, Pp 100382- (2024)

مصطلحات موضوعية: MSM who are eligible for PrEP, PrEP uptake, HIV prevention, Sexual behavior patterns, Latent class analysis, Microbiology, QR1-502, Public aspects of medicine, RA1-1270

الوصف: Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM.Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression.LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as ''top'' in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group.LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2055664024000190Test; https://doaj.org/toc/2055-6640Test

الوصول الحر: https://doaj.org/article/8b6c84861ebb4cc39058f3cf42e4ebceTest

المؤلفون: Jin Wen, Yicheng Zhao, Pu Wu, Yuxuan Liu, Xuntian Zheng, Renxing Lin, Sushu Wan, Ke Li, Haowen Luo, Yuxi Tian, Ludong Li, Hairen Tan

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract Light-induced halide segregation constrains the photovoltaic performance and stability of wide-bandgap perovskite solar cells and tandem cells. The implementation of an intermixed two-dimensional/three-dimensional heterostructure via solution post-treatment is a typical strategy to improve the efficiency and stability of perovskite solar cells. However, owing to the composition-dependent sensitivity of surface reconstruction, the conventional solution post-treatment is suboptimal for methylammonium-free and cesium/bromide-enriched wide-bandgap PSCs. To address this, we develop a generic three-dimensional to two-dimensional perovskite conversion approach to realize a preferential growth of wider dimensionality (n ≥ 2) atop wide-bandgap perovskite layers (1.78 eV). This technique involves depositing a well-defined MAPbI3 thin layer through a vapor-assisted two-step process, followed by its conversion into a two-dimensional structure. Such a two-dimensional/three-dimensional heterostructure enables suppressed light-induced halide segregation, reduced non-radiative interfacial recombination, and facilitated charge extraction. The wide-bandgap perovskite solar cells demonstrate a champion power conversion efficiency of 19.6% and an open-circuit voltage of 1.32 V. By integrating with the thermal-stable FAPb0.5Sn0.5I3 narrow-bandgap perovskites, our all-perovskite tandem solar cells exhibit a stabilized PCE of 28.1% and retain 90% of the initial performance after 855 hours of continuous 1-sun illumination.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/1b1858e5f24649248cbd2ad4d58c1e9dTest

المؤلفون: Yanli Wang, Qiaohuan Deng, Zhenyue Gao, Guangwen Liu, Zhengjie Su, Yicheng Zhao, Lixiu Zhang, Haimiao Yang

المصدر: Frontiers in Pharmacology, Vol 14 (2023)

مصطلحات موضوعية: bioequivalence, pharmacokinetics, renal cell carcinoma, sunitinib, safety, Therapeutics. Pharmacology, RM1-950

الوصف: Purpose: The purpose of this study was to examine the pharmacokinetics (PK), bioequivalence and safety of generic sunitinib and its original product Sutent® in healthy Chinese subjects through a phase-I clinical trial.Methods: The study selected two groups of 24 healthy Chinese subjects in a 1:1 ratio through random allocation. Each participant received either 12.5 mg of sunitinib or Sutent® per cycle. A total of 15 different time points were employed for blood sample collection during each cycle. Furthermore, a comprehensive assessment of the drugs’ safety was consistently maintained throughout the trial.Results: The average adjusted geometric mean ratios (GMR) (90% CI) for the primary PK parameters Cmax, AUC0-t and AUC0-∞ were 97.04% (93.06%–101.19%), 98.45% (93.27%–103.91%) and 98.22% (93.15%–103.56%), respectively. The adjusted GMRs for essential pharmacokinetic (PK) parameters all met the requirements for bioequivalence, with values within the acceptable range of 80%–125%. In addition, the two drugs showed comparable results for the other PK parameters. These results indicate that the two drugs were bioequivalent. Furthermore, both drugs showed well safety.Conclusion: The research results proved that the PK and safety profiles of sunitinib in healthy Chinese subjects were comparable to those of Sutent®. These results advocate the clinical application of generic sunitinib as a potential alternative to original product Sutent® in the treatment of certain medical conditions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2023.1294688/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/9dc2df2f7bf24b7f81c35ac0ba2d6541Test

المؤلفون: Junsheng Luo, Bowen Liu, Haomiao Yin, Xin Zhou, Mingjian Wu, Hongyang Shi, Jiyun Zhang, Jack Elia, Kaicheng Zhang, Jianchang Wu, Zhiqiang Xie, Chao Liu, Junyu Yuan, Zhongquan Wan, Thomas Heumueller, Larry Lüer, Erdmann Spiecker, Ning Li, Chunyang Jia, Christoph J. Brabec, Yicheng Zhao

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-1 (2024)

مصطلحات موضوعية: Science

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/410b61f4550f486c8dd9498cf1f0af7cTest

المؤلفون: Jing Lin, Shihui Sun, Kui Zhao, Fei Gao, Renling Wang, Qi Li, Yanlong Zhou, Jing Zhang, Yue Li, Xinyue Wang, Le Du, Shuai Wang, Zi Li, Huijun Lu, Yungang Lan, Deguang Song, Wei Guo, Yujia Chen, Feng Gao, Yicheng Zhao, Rongrong Fan, Jiyu Guan, Wenqi He

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Science

الوصف: Oncolytic viruses are able to target tumours and thought to induce apoptosis while remodelling the tumour immune microenvironment. Here authors show in an oncolytic parapoxvirus ovis model that pyroptosis, a highly immunogenic Gasdermin-E-dependent cell death mechanism, is the dominant cell death pathway during virotherapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/54598f65320343a09fc60b3d8403744aTest

المؤلفون: Liyan Sui, Yinghua Zhao, Wenfang Wang, Hongmiao Chi, Tian Tian, Ping Wu, Jinlong Zhang, Yicheng Zhao, Zheng-Kai Wei, Zhijun Hou, Guoqiang Zhou, Guoqing Wang, Zedong Wang, Quan Liu

المصدر: Cell & Bioscience, Vol 13, Iss 1, Pp 1-14 (2023)

مصطلحات موضوعية: Flavivirus, Precursor membrane protein, MDA5, MAVS, RLR signaling, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436

الوصف: Abstract Background Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive. Results We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus. Conclusion Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-3701Test

الوصول الحر: https://doaj.org/article/19a613b0e44641828a40da3a940498d6Test

المؤلفون: Shisong Jing, Xinran Ren, Li Wang, Xiangri Kong, Xingye Wang, Xiren Chang, Xuerui Guo, Yan Shi, Jiyu Guan, Tiedong Wang, Bingmei Wang, Wu Song, Yicheng Zhao

المصدر: Virulence, Vol 13, Iss 1, Pp 578-588 (2022)

مصطلحات موضوعية: MRSA, anti-virulence, inhibitor, caseinolytic peptidase P, pneumonia, Infectious and parasitic diseases, RC109-216

الوصف: The resistance of Staphylococcus aureus (S. aureus) to various antibiotics has increased dramatically due to the misuse of antibiotics, and thus the development of new anti-infective drugs with new targets is urgently needed to combat resistance. Caseinolytic peptidase P is a case in hydrolase that regulates the virulence level of S. aureus. Here, we found that nepetin, a small-molecule compound from traditional Chinese herbal flavonoids, effectively inhibits ClpP activity. Nepetin suppressed the virulence of S. aureus and effectively combated the lethal pneumonia caused by MRSA. The results of cellular thermal shift assay showed that nepetin could bind to ClpP and reduce the thermal stability of ClpP, and the KD value of 602 nM between them was determined using localized surface plasmon resonance. The binding mode of nepetin and ClpP was further investigated by molecular docking, and it was found that Ser-22 and Gln-47 of ClpP residues were found to be involved in the binding of nepetin to ClpP. In conclusion, we determined that nepetin is a ClpP inhibitor and an effective lead compound for the development of a virulence factor-based treatment for MRSA infection.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2150-5594Test; https://doaj.org/toc/2150-5608Test

الوصول الحر: https://doaj.org/article/1747e8976e09405198bd0aa09f116e80Test