查找使用阿拉丁产品的科研文献

Quercetin, a flavonoid, suppresses viral proliferation by interfering with the ubiquitin transfer from E1 to E2 enzymes

Hanbo Li,Yu Li,Bowen Yin,Xinming Zhang,Zheng Xu,Changxu Song,Kang Li,Ling Tian

Quercetin is recognized for diverse pharmacological activities. However, the mechanism underlying its broad-antiviral effects has not been elucidated. Herein, we identified quercetin as a potent inhibitor of both double-stranded DNA virus Bombyx mori nucleopolyhedrovirus (BmNPV) and single-stranded RNA virus porcine reproductive and respiratory syndrome virus (PRRSV). Surface plasmon resonance (SPR) revealed that quercetin targets host ubiquitin-activating enzyme 1 (Uba1) homologs. Uba1 knockdown reduced viral proliferation and enhanced the antiviral effect of quercetin, whereas Uba1 overexpression functioned oppositely. Quercetin bound Uba1 homologs with high affinity. Notably, mutation of two binding residues, Q977 and G978, significantly disrupted the binding between BmUba1 and quercetin, and abolished quercetin’s antiviral activity. Quercetin obstructed the transfer of ubiquitin from Uba1 to the E2 enzyme Ubc6, impairing the ubiquitination process. Similarly, quercetin inhibited PRRSV proliferation via targeting Uba1 in mammals. These findings elucidate the molecular mechanism underlying the pharmacological effects of quercetin, providing a theoretical basis for the development of novel antiviral agents against both DNA and RNA viruses. Focusing on BmNPV and PRRSV, this study reveals that quercetin inhibits both DNA and RNA viruses by targeting Uba1 homologs, disrupting ubiquitin transfer between E1 and E2 enzymes. Mutations in key residues on Uba1 impair the binding with quercetin, thus lost the antiviral effect of quercetin. The conserved mechanism across species underscores quercetin’s broad-spectrum antiviral potential, providing a theoretical basis for developing effective antiviral drugs against diverse viral infections.

Construction of microneedle of Atractylodes macrocephala Rhizoma aqueous extract and effect on mammary gland hyperplasia based on intestinal flora

Ping Yang,Gao Qi,Li Changxu,Wang Yan,Wang Yuliang,Li Shuo,Qiu Mingjing,Zhang Linqian,Tu Ailing,Tian Yu,Zhao Hong

Background: A microneedle patch loaded with Atractylodes macrocephala Rhizoma water extract was prepared for the treatment of mammary gland hyperplasia. To explore the relationship between Mammary gland hyperplasia and intestinal flora.Materials and methods: Preparation of the microneedle patch by micromolding method, the prescription of the microneedle was optimized by the Box-Behnken Design response surface test, and the micro-morphology, penetration, toughness, and brittleness were investigated. In vitro release of drug-loaded microneedles was measured by diffusion cell method. The rat model of mammary gland hyperplasia was prepared by the combination of estradiol benzoate-progesterone, and the microneedle patch of Atractylodes macrocephala Rhizoma aqueous extract was used for intervention treatment. The change of levels in E2, P, and PRL in rat serum was determined. The intestinal contents of rats were collected and the changes in intestinal flora in MGH rats were analyzed by 16s rRNA high-throughput sequencing.Results: The optimized microneedle formula is a PVA concentration of 6.0%, HA concentration of 15.5%, and PVPK30 concentration of 16.0%. The prepared microneedle tip loaded with Atractylodes macrocephala Rhizoma aqueous extract has complete, sharp, and no bubbles and the needle rate of the microneedle array is in the range of 95%~100%. The bending rate of the microneedle is about 12.7%, and it has good flexibility, and the microneedle can puncture 4 layers of ParafilmⓇ membrane smoothly, and the puncture rate is more than 96%. The in vitro release of the microneedle was characterized by rapid release. The results of animal experiments showed that Atractylodes macrocephala Rhizoma aqueous extract microneedle patch could significantly reduce the E2 level, significantly reduce the PRL level, and significantly increase the P level. At the same time, it can regulate the abundance and diversity of intestinal flora in MGH rats, improve the intestinal flora disorder caused by mammary gland hyperplasia, and balance the community structure.Conclusion: The prepared microneedle containing Atractylodes macrocephala Rhizoma aqueous extract has good toughness and brittle strength, can penetrate the skin and enter the dermis, and effectively deliver drugs to play a role in the treatment of mammary gland hyperplasia.

Interfacial Electron Transfer Powers Synergistic Fenton-like Oxidation and Enhanced Microbial Metabolism for E2–3S Estrogenic Risk Mitigation

Zhang Wei,Yu Qingmiao,Xue Hongpu,Bao Yi,He Yujie,Geng Jinju

Conjugated estrogens like 17β-estradiol-3-sulfate (E2–3S) are ubiquitous in wastewater and pose latent ecological risks due to their potential conversion into endocrine disruptors. To address the limited removal efficiency of biological treatment and the energy dependence of advanced oxidation processes, we developed a novel biomaterial-coupled system ( P .CE2S–Fe–Zn@NC) to mitigate the estrogenic risks of E2–3S by integrating microbial metabolism with advanced oxidation via interfacial electron transfer. The system achieved a 92.4% reduction in estrogenic activity, significantly outperforming standalone biological (80.2%) and catalytic treatments (38.6%). Mechanistic investigations revealed that the Fe–Zn@NC catalyst established a surface microelectric field that facilitated interfacial electron transfer from bacteria to the catalyst. This electron flux drove a self-sustained Fenton-like reaction, effectively activating bacteria-secreted H 2 O 2 into • OH for oxidative transformation. Concurrently, gene transcriptional changes occurred in the functional bacteria within the coupled system, where the upregulation of respiratory energy metabolism and extracellular electron-transfer genes sustained energy-intensive catabolic processes, specifically desulfation and steroid ring cleavage of E2–3S, as evidenced by upregulated steroid catabolic genes. By synergistically coupling material-driven oxidation with microbe-mediated metabolism, this system reduced the estrogenic activity of the effluent. This study provides a transformative paradigm for bridging microbial bioenergetics with material catalysis, offering a sustainable strategy for remediating latent estrogenic contaminants.

Specific ligands for classical swine fever virus screened from landscape phage display library

Long Yin,Yuzi Luo,Bo Liang,Fei Wang,Min Du,Valery A. Petrenko,Hua-Ji Qiu,Aihua Liu

Classical swine fever (CSF) is a devastating infectious disease caused by classical swine fever virus (CSFV). The screening of CSFV-specific ligands is of great significance for diagnosis and treatment of CSF. Affinity selection from random peptide libraries is an efficient approach to discover ligands with high stability and specificity. Here, we screened phage ligands for the CSFV E2 protein from f8/8 landscape phage display library by biopanning and obtained four phage clones specific for the E2 protein of CSFV. Viral blocking assays indicated that the phage clone displaying the octapeptide sequence DRATSSNA remarkably inhibited the CSFV replication in PK-15 cells at a titer of 10 10 transduction units, as evidenced by significantly decreased viral RNA copies and viral titers. The phage-displayed E2-binding peptides have the potential to be developed as antivirals for CSF.

Chikungunya Virus E2 N218K Enhances Heparan Sulfate-Dependent Attachment and Viral Internalization While Conferring Partial Attenuation in A129 Mice

The E2 glycoprotein of chikungunya virus (CHIKV) binds negatively charged cell-surface heparan sulfate (HS) to facilitate viral attachment and modulate pathogenicity, yet the E2 determinants governing HS-dependent attachment and the effects of altered HS utilization on subsequent infection remain incompletely defined. From a low-passage clinical isolate obtained during the 2010 Guangdong outbreak, we identified a previously unreported E2 substitution, N218K, which introduces a basic residue. In vitro, this mutation enhanced early infection and attachment to mammalian cells and reduced the RNA/PFU ratio; in A129 mice, however, it reduced early serum viral RNA levels, was associated with lower tissue viral RNA burdens at 5 dpi, and delayed mortality, consistent with partial attenuation. Soluble HS competition assays showed that N218K increased HS dependence during viral attachment, whereas DEAE-dextran assays supported a role for charge-dependent interactions in restricting local viral spread. N218K also enhanced viral internalization after normalization of initial attachment, identifying an additional post-attachment phenotype associated with this substitution. Our findings identify N218K as a determinant of HS-dependent attachment and partial attenuation in A129 mice, reveal a “high attachment–low dissemination” phenotype, and further show that this charge-altering E2 substitution enhances post-attachment internalization.

A Novel Estrogen Receptor α-Targeted Near-Infrared Fluorescent Probe for in Vivo Detection of Breast Tumor

Chu Tang,Yang Du,Qian Liang,Zhen Cheng,Jie Tian

The ability to detect breast cancer early in its progression is essential to improve patient survival and quality of life. The noninvasive and dynamic imaging and functional assessments of estrogen receptor-alpha (ERα), which is commonly expressed at high levels in breast cancer, are important for effective diagnosis and treatment. Hence, the development of a specific ERα-targeted probe is a major research goal. To that end, in the present study, we created a novel near-infrared (NIR) fluorescent probe, IRDye800CW–E2, for targeted ERα imaging in breast-tumor-bearing mice. IRDye800CW–E2 consisted of a cyanine dye IRDye800CW as the NIR fluorophore and the E2 analogue ethinyl estradiol amine as an ERα targeting ligand. The ethinyl estradiol amine was initially labeled with fluorescein isothiocyanate (FITC) to evaluate the binding specificity to human breast-tumor cells in vitro. Flow chamber and in vitro confocal laser endomicroscopy imaging experiments demonstrated that FITC–E2 was specifically taken up by MCF-7 cells. Furthermore, NIR fluorescence imaging revealed the ability of IRDye800CW–E2 to rapidly target tumors and to achieve good contrast between tumors and background signal 4–48 h postinjection. The fluorescent signal of IRDye800CW–E2 in tumors was successfully blocked by the coinjection of the endogenous ERα-ligand 17β-estradiol (E2) and the probe. Ex vivo fluorescent imaging further confirmed high uptake of the probe by tumors. These results indicated that IRDye800CW–E2 has great potential as an ERα-targeted imaging probe for early breast-tumor detection and has potential for clinical translation.

Simultaneously responsive microfluidic chip aptasensor for determination of kanamycin, aflatoxin M1, and 17β-estradiol based on magnetic tripartite DNA assembly nanostructure probes

He Liyong,Shen Zhipeng,Wang Jiaqi,Zeng Jin,Wang Wenhai,Wu Huihui,Wang Qiqin,Gan Ning

The authors describe a microfluidic chip-based aptasensor platform combined with magnetic tripartite DNA structure-functionalized nanocomposites to achieve simultaneous determination of kanamycin (KANA), aflatoxin M1 (AFM1), and 17β-estradiol (E2) in milk. The two-duplex tripartite DNA nanostructure was first assembled on the surface of magnetic beads. When the aptamer on the probes recognized the specific target, the aptamer-target would be released into the supernatant. The pre-primer@circular DNA template structure initiates rolling circle amplification (RCA) by phi29 polymerase. After magnetic separation, the magnetic nanocomposites were added into a solution containing three different lengths of complementary strands to the RCA products. The number of complementary strands significantly decrease, and this can be quantitated by the microfluidic chip. Further, the employment of magnetic nanocomposites and microfluidic chip not only resolve the complex matrix interference, but also dramatically enhances the determination selectivity and sensitivity. This aptasensor allows for determination of KANA, AFM1, and E2 with limits of detection as low as 0.32 pg mL −1 , 0.95 pg mL −1 , and 6.8 pg mL −1 , respectively. This novel method exhibits the advantages of excellent stability and fast response time (< 3 min on microfluidic chip platform) for simultaneous determination of KANA, AFM1, and E2 in milk samples and ensures food safety. Graphical abstract

Ratiometric electrochemiluminescence biosensor for hepatitis C virus E2 protein based on block copolymers-solubilized Ir(ppy)3 with high electrochemiluminescence efficiency

Yitian Huang,Dandan Zhao,Yanjie Chen,Shupei Zhang,Feng Lin,Hong Dai

Iridium (Ir) complexes have gained remarkable development momentum as candidates for electrochemiluminescence , but their poor solubility in water media greatly limited their application in ECL area. Herein, a facile nanoprecipitation method by encapsulating tris(2-phenylpyridinato)iridium (Ir(ppy) 3 ) into pluronic block copolymers for preparing water-soluble Ir(III) complexes with high ECL emission efficiency was developed. Then, with F-127@Ir(ppy) 3 as the anode emitter and g-C 3 N 4 as the cathode emitter, a new ratiometric biosensor based on transition metal complexes was developed for the first time, which was used for ultra-sensitive detection of hepatitis C virus E2 protein. Notably, the ratiometric ECL signal could be mediated by using multifunctional Nb 2 C nanosheets (Nb 2 C NSs) with excellent electrocatalytic activity and superoxide dismutase activity, so as to enhance the ECL intensity of anode and quench the response of cathode ECL. Combining Nb 2 C NSs with the antibody and the specific recognition process, the proposed ECL ratio biosensor showed good performance for E2 with a linear range from 1 × 10 −3  ng/mL to 1 × 10 2  ng/mL and a detection limit of 8.39 × 10 −4  ng/mL. The work on designing water-soluble Ir (III) complexes with pluronic block copolymer provides an ingenious approach to broaden the application of poorly soluble complexes in bioassays.

Hydrogen Sulfide Improves Functional Recovery in Rat Traumatic Spinal Cord Injury Model by Inducing Nuclear Translocation of NF-E2-Related Factor 2

Chang Xu,Man Zhang,Guangping Zhang,Sheng Yan,Weiqi Yan

Hydrogen sulfide (H2S), an important gaseous messenger, is known to have neuroprotective effects in many neurological disorders. This study examined the neuroprotective effects and the associated mechanisms of H2S in the model Sprague–Dawley (SD) rats with spinal cord injury (SCI). We found that H2S showed neuroprotective effects in SCI model rats, improved the symptoms of neurological impairment, reduced the secretion of inflammatory factors, nerve cell apoptosis, and endoplasmic reticulum (ER), and oxidative stresses. Moreover, these effects were produced by activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Our results suggest that H2S supplementation could be a potential therapeutic strategy to promote SCI recovery.

Nrf2 deficiency aggravates Angiotensin II-induced cardiac injury by increasing hypertrophy and enhancing IL-6/STAT3-dependent inflammation

Dandan Chen,Zhe Li,Peiqing Bao,Miao Chen,Miao Zhang,Fangrong Yan,Yitao Xu,Caoyu Ji,Xinyue Hu,Daniel Sanchis,Yubin Zhang,Junmei Ye

Background NF-E2-related factor 2 (Nrf2) is a transcription factor playing cytoprotective effects in various pathological processes including oxidative stress and cardiac hypertrophy. Despite being a potential therapeutic target to treat several cardiomyopathies, the signaling underlying Nrf2-dependent cardioprotective action remains largely uncharacterized. Aim This study aimed to explore the signaling mediating the role of Nrf2 in the development of hypertensive cardiac pathogenesis by analyzing the response to Angiotensin II (Ang II) in the presence or absence of Nrf2 expression, both in vivo and in vitro. Results Our results indicated that Nrf2 deficiency exacerbated cardiac damage triggered by Ang II infusion. Mechanistically, our study shows that Ang II-triggered hypertrophy and inflammation is exacerbated in the absence of Nrf2 expression and points to the involvement of the IL-6/STAT3 signaling pathway in this event. Indeed, our results show that IL-6 abundance triggered by Ang II is increased in the absence of Nrf2 and demonstrate the requirement of IL-6 in STAT3 activation and cardiac inflammation induced by Ang II. Conclusion Our results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.

Preparation and Characterization of a Novel Aspirin Derivative with Anti-Thrombotic and Gastric Mucosal Protection Properties

Xi-E Zhen,Ming Zong,Sai-Nan Gao,Yong-Gang Cao,Lei Jiang,Shu-Xin Chen,Kuan Wang,Shi-Qin Sun,Hai-Sheng Peng,Yu-Hua Bai,Sen Li

The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca 2+ ). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

Production of renewable 1,3-pentadiene over LaPO4 via dehydration of 2,3-pentanediol derived from 2,3-pentanedione

Ruilin Feng,Yanlong Qi,Shijun Liu,Long Cui,Quanquan Dai,Chenxi Bai

1,3-Pentadiene plays an extremely important role in the production of polymers and fine chemicals. Herein, the LaPO 4 catalyst exhibits excellent catalytic performance for the dehydration production of 1,3-pentadiene with 2,3-pentanediol, a C5 diol platform compound that can be easily obtained by hydrogenation of bio-based 2,3-pentanedione. The relationships of catalyst structure-acid/base properties-catalytic performance was established, and an acid-base synergy effect was disclosed for the on-purpose synthesis of 1,3-pentadiene. Thus, a balance between acid and base sites was required, and an optimized LaPO 4 with acid/base ratio of 2.63 afforded a yield of 1,3-pentadiene as high as 61.5% at atmospheric pressure. Notably, the Brønsted acid sites with weak or medium in LaPO 4 catalyst can inhibit the occurrence of pinacol rearrangement, resulting in higher 1,3-pentadiene production. In addition, the investigation on reaction pathways demonstrated that the E2 mechanism was dominant in this dehydration reaction, accompanied by the assistance of E1 and E1cb.